Effect of porcine gastrin releasing peptide on gastric secretion and motility and the release of hormonal peptides in conscious cats.

PubMed

Vagne, M; Collinet, M; Cuber, J C; Bernard, C; Chayvialle, J A; McDonald, T J; Mutt, V

1987-01-01

The effect of porcine gastrin releasing peptide (GRP) was compared to those of bombesin (BBS) and pentagastrin (PG) in conscious cats. GRP and BBS augmented acid and pepsin secretions, as well as antral motility with an early effect comparable to that produced by pentagastrin with an elevation of low amplitude contractions and a diminution of high amplitude contractions. BBS and GRP increased plasma gastrin and pancreatic polypeptide (PP) levels and decreased motilin levels measured by a C terminus-directed antiserum. In all cases, BBS and GRP displayed parallel dose-response curves. PG showed slight differences in the slopes of the dose-response curves slopes of the dose-response curves except for acid secretion stimulation where no difference was noted (PG was the most effective) and for pepsin stimulation where the difference was large (PG was much less effective). According to the different targets studied, BBS was 4 to 9 times more potent than GRP, 6 to 200 times more than PG. Gastrin release, elicited by the lowest ED50 of both BBS and GRP, should be considered as their primary effect in the cat.

Development of a canine model to enable the preclinical assessment of pH-dependent absorption of test compounds.

PubMed

Fancher, R Marcus; Zhang, Hongjian; Sleczka, Bogdan; Derbin, George; Rockar, Richard; Marathe, Punit

2011-07-01

A preclinical canine model capable of predicting a compound's potential for pH-dependent absorption in humans was developed. This involved the surgical insertion of a gastrostomy feeding tube into the stomach of a beagle dog. The tube was sutured in position to allow frequent withdrawal of gastric fluid for pH measurement. Therefore, it was possible to measure pH in the stomach and assess the effect of gastric pH-modifying agents on the absorption of various test compounds. Fasted gastric pH in the dog showed considerable inter- and intra-animal variability. Pretreatment of pentagastrin (6 µg/kg intramuscularly) 20 min prior to test compound administration was determined to be adequate for simulating fasting stomach pH in humans. Pretreatment with famotidine [40 mg orally] 1 h prior to test compound administration was determined to be adequate for simulating human gastric pH when acid-reducing agents are coadministered. Pentagastrin and famotidine pretreatments were used to test two discovery compounds and distinct differences in their potential for pH-dependent absorption were observed. The model described herein can be used preclinically to screen out compounds, differentiate compounds, and support the assessment of various formulation- and prodrug-based strategies to mitigate the pH effect. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

[Potentiating effect of sodium glutamate on gastric secretion and its possible use as a clinical test].

PubMed

Shlygin, G K; Vasilevskaia, L S; Loranskaia, T I; Shakhovskaia, A K; Lebedeva, R P

1991-08-01

The authors report a potentiating effect of sodium glutamate on gastric secretion in subjects free of gastrointestinal diseases. Similar effect has been discovered in dogs. In subjects with gastric hyposecretion (chronic gastritis, functional regulatory disturbances) sodium glutamate combined with pentagastrin is a helpful tool in overall evaluation of gastric secretion. In achlorhydria is can be used for determination of a residual capacity of the stomach to secrete the hydrochloric acid in failure of humoral stimulators.

[Effects of IGN-2098, a new histamine H2-receptor antagonist, on gastric secretion and gastric and duodenal lesions induced in rats. Comparison with roxatidine].

PubMed

Okabe, S; Narita, M; Nakaji, S; Takinami, Y; Kawano, O; Misaki, N

1992-03-01

A new compound, IGN-2098 [5,6-dimethyl-2-[4-<3-(1-piperidinomethyl) phenoxy>cis-butenylamino]-4-(1H)-pyrimidone.2HCl], was found to be a potential histamine H2-receptor antagonist in the guinea pig atrium. IGN-2098, given p.o., significantly and persistently (for more than 12 hr) inhibited the basal gastric secretion in pylorus-ligated rats. The agent also significantly inhibited the basal gastric secretion when given by the s.c.-, i.d.- or i.p.-route. Stimulated gastric secretion in fistula rats in response to histamine, carbachol or pentagastrin was also significantly inhibited with IGN-2098 given s.c. Pretreatment with IGN-2098 (p.o.) significantly protected the gastric mucosa against pylorus ligation-, water-immersion stress-, histamine-, indomethacin-, HCl.aspirin-, and HCl.ethanol-induced gastric lesions. In addition, the agent significantly protected the duodenal mucosa against mepirizole-induced ulcers. Based upon the ED50 values, the antisecretory effects on histamine, carbachol or pentagastrin-stimulated acid secretion were 6.0, 37.0 or 80 times more potent than roxatidine, respectively. As to the anti-lesion effects on HCl.aspirin-induced gastric lesions or mepirizole-induced duodenal ulcers, IGN-2098 was 8.1 or 14.8 times more potent than roxatidine, respectively. These results suggest that IGN-2098 will be a useful drug for the treatment of gastric and duodenal lesions in man.

[The use of monosodium glutamate in the combined therapy of patients with atrophic gastritis].

PubMed

Kochetkov, A M; Shlygin, G K; Loranskaia, T I; Vasilevskaia, L S; Kondrashev, S Iu

1992-01-01

Monosodium glutamate (MSG) taken per os has been found to stimulate gastric secretion provoked by pentagastrin. MSG gave rise to a marked elevation of endogenic gastrin levels both in experimental animals and atrophic gastritis patients. Thirty-six patients with secretory gastric insufficiency received MSG as an additive to their food during combined therapy of their disease. The preparation proved to be well-tolerated, good stimulant of gastric secretion, efficient in digestion improvement. MSG is recommended as an adjuvant in combined therapy of atrophic gastritis.

Gastric antisecretory role and immunohistochemical localization of cannabinoid receptors in the rat stomach

PubMed Central

Adami, Maristella; Frati, Paolo; Bertini, Simone; Kulkarni-Narla, Anjali; Brown, David R; Caro, Giuseppe de; Coruzzi, Gabriella; Soldani, Giulio

2002-01-01

The role of cannabinoid (CB) receptors in the regulation of gastric acid secretion was investigated in the rat by means of functional experiments and by immunohistochemistry. In anaesthetized rats with lumen-perfused stomach, the non selective CB-receptor agonist WIN 55,212-2 (0.30 – 4.00 μmol kg−1, i.v.) and the selective CB1-receptor agonist HU-210 (0.03 – 1.50 μmol kg−1, i.v.), dose-dependently decreased the acid secretion induced by both pentagastrin (30 nmol kg−1 h−1) and 2-deoxy-D-glucose (1.25 mmol kg−1, i.v.). By contrast, neither WIN 55,212-2 (1 – 4 μmol kg−1, i.v.) nor HU-210 (0.03 – 1.50 μmol kg−1, i.v.) did modify histamine-induced acid secretion (20 μmol kg−1 h−1). The selective CB2-receptor agonist JWH-015 (3 – 10 μmol kg−1, i.v.) was ineffective. The gastric antisecretory effects of WIN 55,212-2 and HU-210 on pentagastrin-induced acid secretion were prevented by the selective CB1-receptor antagonist SR141716A (0.65 μmol kg−1, i.v.) and unaffected by the selective CB2-receptor antagonist SR144528 (0.65 – 2 μmol kg−1, i.v.). Bilateral cervical vagotomy and ganglionic blockade with hexamethonium (10 mg kg−1, i.v., followed by continuous infusion of 10 mg kg−1 h−1) significantly reduced, but not abolished, the maximal inhibitory effect of HU-210 (0.3 μmol kg−1, i.v.) on pentagastrin-induced acid secretion; by contrast, pretreatment with atropine (1 mg kg−1, i.v.) did not modify the antisecretory effect of HU-210. Immunoreactivity to the CB1 receptor was co-localized with that of the cholinergic marker choline acetyltransferase in neural elements innervating smooth muscle, mucosa and submucosal blood vessels of rat stomach fundus, corpus and antrum. In contrast, CB2 receptor-like immunoreactivity was not observed. These results indicate that gastric antisecretory effects of cannabinoids in the rat are mediated by suppression of vagal drive to the stomach through activation of CB1 receptors, located on pre- and postganglionic cholinergic pathways. However, the ineffectiveness of atropine in reducing the effect of HU-210 suggests that the release of non cholinergic excitatory neurotransmitters may be regulated by CB1 receptors. PMID:11934799

Effect of gastrointestinal hormones on the biliary sphincter of the opossum.

PubMed

Becker, J M; Moody, F G; Zinsmeister, A R

1982-06-01

The smooth muscle sphincter enveloping the terminal portion of the common bile duct in the opossum exhibits spontaneous electrical activity and simultaneous rhythmic contractions. The aim of our study was to define the influence of four gastrointestinal hormones on biliary sphincter electrical and mechanical activity. An array of five monopolar extracellular electrodes was placed along the opossum choledochal sphincteric smooth muscle and contiguous duodenum. A catheter in continuity with a pressure transducer, drop counter, and saline reservoir was placed in the common duct for simultaneous measurement of ductal pressure and flow. The cystic and distal common hepatic ducts were then ligated to isolate the common bile duct from the gallbladder and liver. In each opossum, biliary sphincteric and duodenal myoelectric activity, common bile duct and gallbladder pressure, and common duct flow were recorded simultaneously before and after the intravenous administration of five different doses of an enteric hormone. Ten animals were given 0.1-10.0 international dog units per kilogram body wt of cholecystokinin, 10 received 0.01-1.00 microgram/kg body wt of cholecystokinin-octapeptide, 10 were given 0.1-10.0 micrograms/kg body wt of secretin, and 5 were given 0.1-10.0 micrograms/kg body wt of pentagastrin. Cholecystokinin, cholecystokinin-octapeptide, and pentagastrin all effected a significant increase in sphincter electrical spike activity and common duct pressure with a decrease in common duct flow. This contractile response was consistent at a wide range of hormonal levels. Secretin had little effect on biliary pressure, flow, and myoelectric activity. The data lend support to the concept that cholecystokinin and gastrin contract the biliary sphincter, metering bile flow at the time of gallbladder emptying in the opossum.

Impaired viscosity of gastric secretion and its mucin content as potential contributing factors to the development of chronic constipation.

PubMed

Castro-Combs, Juan; Garcia, Cesar J; Majewski, Marek; Wallner, Grzegorz; Sarosiek, Jerzy

2014-11-01

The alimentary tract mucosa continuously releases mucus-rich secretion. Mucin, the major component of mucus, determines its viscosity and provides lubrication for the luminal content of indigestible food particles. To measure mucin secretion rate and its viscosity in patients with chronic constipation (CC) and in asymptomatic volunteers. Nineteen patients with symptoms of CC and 19 controls were included in the study. Mucin secretion and viscosity were assessed in aspirated gastric juice in basal conditions and after stimulation with pentagastrin (1 h each). Mucin content was tested by PAS methodology. Viscosity was measured using cone/plate digital viscometer. Mucin secretion rates in basal and stimulated conditions in controls were 65 and 42 % higher than in patients with CC (P < 0.05 and P < 0.001, respectively). Basal viscosity in controls was 48 % higher than in CC (P < 0.05) at the lowest and 55 % higher (P < 0.05) at the middle velocities. Viscosity in pentagastrin-stimulated conditions in controls was 71 % higher than in CC (P < 0.01) at the lowest and 35 % higher (P < 0.05) at the middle velocities. (1) The significantly lower rate of soluble mucin secretion in patients with CC than in normal volunteers may reflect impairment in mucin-related lubrication. (2) Significantly lower viscosity of gastric secretion in patients with CC may result from the lower rate of mucin secretion and may also diminish lubrication within the alimentary tract. (3) This may potentially set the stage for the development of symptoms related to chronic constipation and open a new therapeutic avenue for this patient population.

[The effect of bombesin and its analogs on the secretion of gastric juice and its content of pepsin and hydrochloric acid].

PubMed

Barashkova, G M; Klimov, P K; Kuranova, I L; Churkina, S I; Filonova, E B

1990-07-01

I.V. Infusion of bombesine after eating raw meat inhibited for 30-60 min the secretion of gastric juice and hydrochloric acid in dogs. Within 90-120 min of simultaneous infusion of pentagastrin and bombesine, the amount of secreted juice and its acidity decreased and then the secretion of gastric parietal cells increased. Simultaneous infusion of histamine and bombesine increased the response of gastric parietal cells during the whole experiment as compared with the histamine effect alone. Microapplication of bombesine into cerebral structures also decreased the secretory response of the parietal cells.

Pernicious anemia: What are the actual diagnosis criteria?

PubMed Central

Cattan, Daniel

2011-01-01

A gastric intrinsic factor output under 200 U/h after pentagastrin stimulation (N > 2000 U/h) is specific for pernicious anemia. The other findings are either variable or non specific. Serum intrinsic factor antibodies, considered as specific in general practice, are present only in half of the patients with pernicious anemia. In their absence, since the disappearance of the Schilling tests, the gastric tubage currently used for the study of gastric acid secretion, is obligatory for the simultaneous study of intrinsic factor output. This study is important to eliminate another disease much more frequent than pernicious anemia, the protein bound to cobalamin malabsorption was observed in achlorhydric simple atrophic gastritis in the presence of intrinsic factor secretion. PMID:21274387

Pernicious anemia: what are the actual diagnosis criteria?

PubMed

Cattan, Daniel

2011-01-28

A gastric intrinsic factor output under 200 U/h after pentagastrin stimulation (N > 2000 U/h) is specific for pernicious anemia. The other findings are either variable or non specific. Serum intrinsic factor antibodies, considered as specific in general practice, are present only in half of the patients with pernicious anemia. In their absence, since the disappearance of the Schilling tests, the gastric tubage currently used for the study of gastric acid secretion, is obligatory for the simultaneous study of intrinsic factor output. This study is important to eliminate another disease much more frequent than pernicious anemia, the protein bound to cobalamin malabsorption was observed in achlorhydric simple atrophic gastritis in the presence of intrinsic factor secretion.

Calcitonin assay in wash-out fluid after fine-needle aspiration biopsy in patients with a thyroid nodule and border-line value of the hormone.

PubMed

Massaro, F; Dolcino, M; Degrandi, R; Ferone, D; Mussap, M; Minuto, F; Giusti, M

2009-04-01

Assaying calcitonin (CT) in the wash-out fluid from fine-needle aspiration biopsies (CT-FNAB) could be useful in the diagnosis of medullary thyroid carcinoma (MTC). The aim of this study was to correlate serum CT with cytology and CT-FNAB. Twenty-seven subjects (age range 27-75 yr) were studied. FNAB was performed in a thyroid nodule (no.=16) or lymph-node (no.=1 previously operated on for MTC) or in the prevalent nodule of multinodular goiters (no.=10). CT-FNAB values obtained in 37 subjects with normal serum CT (<10 ng/l) who underwent FNAB for thyroid nodules served as a negative control. In these subjects, CTFNAB values were 8.2+/-6.4 ng/l (range 2-30 ng/l). In patients with a thyroid nodule under evaluation for MTC, serum CT and CT-FNAB values were 14.5+/-3.9 ng/l (range 10-24 ng/l) and 16.4+/-29.8 ng/l (range 2-144 ng/l), respectively. In 4 patients, CT-FNAB values were higher than the highest values found in our negative controls (30 ng/l), but cytology results were compatible with a benign thyroid lesion and pentagastrin testing was negative. In 3 cases with CT-FNAB <30 ng/l, cytology was indicative of an indeterminate or probably follicular malignant lesion and histology was negative for MTC. None of the other subjects in whom pentagastrin testing was conducted showed serum CT values >100 ng/l. Our data do not show any correlation between CT-FNAB and serum CT. In conclusion, borderline CT values in patients with thyroid nodules are not rare. Our experience suggests that CT-FNAB does not have the same importance as that reported in the literature for thyroglobulin and PTH assay in wash-out fluid after FNAB in malignant thyroid and hyperfunctioning parathyroid lesions.

Gastric secretory function in coeliac disease.

PubMed

Marcello, U; Deganello, A; Consolaro, G; Zoppi, G

1979-01-18

Volume, total titrable acidity, total proteolytic activity and pepsin activity have been determined in 14 coeliac patients and in 8 controls of comparable ages and body weights. Basal secretion (B.O.), total outputs (T. O.) and peak outputs (P.O.) after pentagastrin injection have been determined. Peak outputs (values 60 min/kg) of these parameters are as follows: volume 5.0+/-1.7 ml in coeliacs, 4.3+/-1.2 ml in controls; total titrable acidity 406.1+/-155.0 mEq in patients, 296.1+/-182.4 in conttrols; total proteolytic activity 962.1+/-501.1 micronEq in coeliacs, 569.6+/-272.2 in controls; pepsin activity 789.1+/-521.8 micronEq in patients, 447.6+/-150.4 in controls.

[The value of the thermocouple in the measurement of the gastric mucosal blood-flow. The influence of the occlusion of the celiac artery and prostaglandin E1 on the gastric mucosal blood flow. An experimental study in animals (author's transl)].

PubMed

Koch, H; Demling, L

1976-02-27

The study has been carried out to ensure the positive evidence of the measurement of the gastric mucosal blood-flow with the aid of the thermocouple (heat-clearance technique). The experiments have shown that the suction pressure of 600 mm mercury column which was used to fix the Thermocouple to the mucosa was indispensable in order to assess the blood-flow in the entire depth of the mucosa. Changes in the mucosal blood-flow are measuured at the same rate in all quadrants of the gastric corpus. The measuring of the blood-flow of a well circumscribed area of the mucosa is therefore representative for the entire corpus. Vasopressin led to a significant reduction of the gastric mucosal blood-flow measured with heat-clearance as well aminopyrine-clearance. There was a linear correlation between the results of both methods. Vasopressin selectively reduces the blood-flow of the gastric mucosa but not of the submucosa, the muscular layer and the serosa. Therefore it seems to be probable that changes in mucosal blood-flow selectively can be measured with the aid of the thermocouple. After previous stimulation with pentagastrin neither mucosal blood-flow nor acid secretion of the stomach were influenced by the occlusion of the celiac artery by 25 %. The occlusion of the celiac artery by 50 % reduced significantly the pentagastrin-stimulated gastric mucosal blood-flow whereas the acid secretion was not influenced. Prostaglandin E1 at a dose rate of 2 mug/kg-h increased significantly arterial and mucosal blood-flow as well as acid secretion of the stomach. In comparison PGE1 administered at a dose rate of 4 mug/kg-h reduced significantly gastric mucosal blood-flow and gastric secretion. PGE1 at a dose rate of 8 mug/kg-h did not produce any significant changes in blood-flow and secretion. The results suggested that the changes of gastric secretion observed with PGE1 were the consequence of primary changes in the gastric mucosal blood-flow.

Potentiation of the gastric antisecretory activity of histamine H2-receptor antagonists by clebopride.

PubMed

Fernández, A G; Massingham, R; Roberts, D J

1988-05-01

The substituted benzamide, clebopride, at doses (0.03-3 mg kg-1 i.p.) that were without effect per se on the secretion of gastric acid in pylorus ligated (Shay) rats, potentiated the antisecretory effects of the histamine H2 receptor antagonists cimetidine and ranitidine in this model but not those of the muscarine receptor antagonist pirenzepine nor those of the proton pump inhibitor omeprazole. By contrast, clebopride was without influence on the inhibitory effects of cimetidine on pentagastrin-induced secretion in perfused stomach (Ghosh and Schild) preparations in anaesthetized rats. The significance of these findings is discussed in relation to the previously described potentiating effects of clebopride on the anti-ulcer activity of cimetidine in various experimental models, and the potential beneficial effects of such combined therapy in the clinic.

Effects of gonadotropin-releasing hormone (GnRH) on gastric secretion and gastrin release in the dog.

PubMed

Soldani, G; Del Tacca, M; Bambini, G; Polloni, A; Bernardini, C; Martinotti, E; Martino, E

1982-01-01

The effects of GnRH on gastric secretion and gastrin release from dogs provided with gastric fistulae and Heidenhain pouches have been investigated. A transient yet significant inhibition of pentagastrin-stimulated secretion from gastric fistulae was observed, while secretion from Heidenhain pouches was unchanged. The maximal inhibitory effect of GnRH on both acid and pepsin secretion stimulated by 2-deoxy-D-glucose was obtained from gastric fistulae. On the contrary, GnRH failed to affect either acid secretion stimulated by bethanechol or acid secretion and gastrin release induced by bombesin. The present results indicate that GnRH possesses an inhibitory action on gastric secretion from the vagally innervated stomach of the dog. The most likely inhibitory mechanism seems to be represented by a decrease of the vagal activity.

[Effect of glutamate and combined with inosine monophosphate on gastric secretion].

PubMed

Vasilevskaia, L S; Rymshina, M V; Shlygin, G K

1993-01-01

Experiments on dogs with Pavlov pouch and gastric fistula demonstrate that monosodium glutamate (MSG) enriched with inosine monophosphate (IMP) potentiate pentagastrin-induced gastric secretion. The preparation (Chi-Mi) was introduced directly into the intestine through a fistula. When given alone in an equal quantity MSG produced the same effect. In per os administration Chi-Mi was more effective, probably due to a different response of the gustatory receptors to MSG and Chi-Mi. When the latter two were added to meat used as a food stimulus, Chi-Mi brought about more intensive gastric secretion in all its phases. In sham feeding Chi-Mi also intensified the secretion augmenting the reflex phase of gastric secretion when added to food substances. The findings may appear helpful in further search for medical application of glutamate and allied substances.

[THe characteristics of the action of Khi-Mi on gastric and hepatic secretion].

PubMed

Rymshina, M V; Vasilevskaia, L S

1996-01-01

The peculiarities of action of He-Me (92% of sodium glutamate and 8% sodium inosinemonophosphate) on gastric and liver secretions was studied in experiments on dog with Pavlov's isolated ventricle and dogs with bile duct, taken out on the skin (operation by M. F. Nesterin). He-Me exerted promotional influence on gastric secretion provoked by pentagastrin increasing of secretion by 3-5 times with prolongation of secretion time. The gastric secretion in various stages (nervous, secretory, intestinal) was strengthened after adding of He-Me to dietary meat. In that way effect of He-Me on gastric secretion is the same as effect of sodium glutamate but effect He-Me more strong after oral intake. He-Me has also choleretic effect. The data allow to re recommend He-Me as diagnostic and therapeutic remedy.

Urea and ammonia excretion into gastric juice in regularly dialyzed patients and patients after renal transplantation. I. Dialyzed patients.

PubMed

Skála, I; Marecková, O; Růzicková, J; Bláha, J; Straková, M; Reneltová, I; Jirka, J; Kocandrle, V; Zvolánková, K

1978-01-01

In regularly dialyzed patients in basal gastric juice and after stimulation with pentagastrin the volume of titrable acidity, urea and ammonia were assessed. It was revealed that in relation to the plasma urea concentration in basal juice the mean urea and ammonia concentration is roughly half and in stimulation juice roughly one third. The urea concentration in gastric juice is negatively correlated to the ammonia concentration. Urea excretion into the stomach depends on the plasma urea level and on the secretory gastric activity. The decisive factor of gastric secretion is probably parietal cell secretion. From the results ensues that gastric juice of dialyzed patients contains a quantitatively significant amount of urea and ammonia. Ammonia due to its neutralizing action distorts the examination of gastric acidity assessed by titration. The findings call for a revision of hitherto known data concerning gastric secretion of uraemic patients.

Pharmacological constriction of the lower oesophageal sphincter: a simple method of arresting variceal haemorrhage.

PubMed Central

Hosking, S W; Doss, W; el-Zeiny, H; Robinson, P; Barsoum, M S; Johnson, A G

1988-01-01

The effect of pharmacological constriction of the lower oesophageal sphincter (LOS) on oesophageal varices was investigated in an experimental study followed by a controlled clinical trial. In the experimental study intravariceal pressure was measured just above the LOS in 11 patients before and after constricting the LOS by intravenous pentagastrin. Intravariceal pressure fell from a mean of 23 (range 12-36) mmHg to 4 (range 0-7) mmHg (p less than 0.001). This marked pressure drop indicated the considerable compression of varices that occurred within the LOS. A prospective controlled clinical trial examined whether LOS constriction (effected by the longer acting metoclopramide) would compress varices sufficiently to arrest active variceal bleeding originating from the lowest 2 cm oesophagus--the area encircled by the LOS. Of 11 patients who received metoclopramide, 10 stopped bleeding compared with four of the 11 who received placebo (p less than 0.01). Pharmacological constriction of the LOS appears to offer a new and effective approach for arresting active bleeding from oesophageal varices. PMID:3044932

An Inhibitory Innervation at the Gastroduodenal Junction

PubMed Central

Anuras, Sinn; Cooke, Allan R.; Christensen, James

1974-01-01

Transverse muscle strips, 2-mm wide, were cut serially from the gastroduodenal junction in opossums, cats, dogs, and man. Electrical field stimulation with trains of rectangular current pulses of 0.5 ms in all opossums, all cats, some dogs, and the one human specimen induced relaxation in strips from the thickened circular muscle proximal to the mucosal junction. In some opossums weak relaxations also occurred in the first few strips below the mucosal junction. All other strips contracted or showed no response. This relaxation in opossums was abolished by tetrodotoxin but was not affected by antagonists to adrenergic and cholinergic transmission, nor by tripelennamine, methysergide, pentagastrin, secretin, cerulein, or cholecystokinin. Optimal frequency for stimulus-relaxation was 12 Hz. Chronaxie was 0.85 ms. The junctional strips also showed greater resistances to stretch than those remote from the junction. With apparent species variations, the junctional muscle possesses a nonadrenergic inhibitory innervation which is either absent or unexpressed in adjacent muscle of stomach and duodenum. This suggests the existence of a distinctive inhibitory neural control mechanism for pyloric muscle. Images PMID:4152775

Oxytocin binding sites in bovine mammary tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Xin.

1989-01-01

Oxytocin binding sites were identified and characterized in bovine mammary tissue. ({sup 3}H)-oxytocin binding reached equilibrium by 50 min at 20{degree}C and by 8 hr at 4{degree}C. The half-time of displacement at 20{degree}C was approximately 1 hr. Thyrotropin releasing hormone, adrenocorticotropin, angiotensin I, angiotensin II, pentagastrin, bradykinin, xenopsin and L-valyl-histidyl-L-leucyl-L-threonyl-L-prolyl-L-valyl-L-glutamyl-L-lysine were not competitive. In the presence of 10 nM LiCl, addition of oxytocin to dispersed bovine mammary cells, in which phosphatidylinositol was pre-labelled, caused a time and dose-dependent increase in radioactive inositiol monophosphate incorporation. The possibility that there are distinct vasopressin receptors in bovine mammary tissue was investigated. ({sup 3}H)-vasopressinmore » binding reached equilibrium by 40 min at 20{degree}. The half-time of displacement at 20{degree}C was approximately 1 hr. The ability of the peptides to inhibit ({sup 3}H)-vasopressin binding was: (Thr{sup 4},Gly{sup 7})-oxytocin > Arg{sup 8}-vasopressin > (lys{sup 8})-vasopressin > (Deamino{sup 1},D-arg{sup 8})-vasopressin > oxytocin > d (CH{sub 2}){sub 5}Tyr(Me)AVP.« less

Stimulation of Mucin, Mucus, and Viscosity during Lubiprostone in Patients with Chronic Constipation may Potentially Lead to Increase of Lubrication.

PubMed

Majewski, Marek; Sarosiek, Irene; Wallner, Grzegorz; Edlavitch, Stanley A; Sarosiek, Jerzy

2014-12-18

The purpose of this clinical trial was to explore whether lubiprostone increases the rate of mucus and mucin secretion and its viscosity in chronic constipation (CC) patients. The secretion of chloride (CS) into the gastrointestinal tract lumen is pivotal in the body's ability to process non-digestible food components. CS sets the optimal rate of hydration for non-digestible food components, their fluidity, and their adequate propulsion along the alimentary tract. Chloride is also instrumental in the secretion of alimentary tract mucus, and the formation of a gel-like, viscous mucus-buffer layer. This layer acts as the first line and vanguard of the mucosal barrier. This barrier is essential in mucosal lubrication and protection. Lubiprostone, a novel chloride channel stimulator ClC-2, is currently approved for the treatment of CC. Its impact on mucus, mucus secretion, and viscosity is not established. A double-blind, crossover trial was approved by the IRBs at the Kansas University Medical Center (Kansas City, KS) (study site) and at the Texas Tech University HSC (El Paso, TX) (analysis site). The study included 20 patients (17 females (F); mean age: 37 years) with symptoms of CC diagnosed according to the Rome III criteria. Patients were randomized to 1 week of therapy with lubiprostone or placebo followed by a 1 week washout and 1 week of the alternative therapy. Gastric juice was collected basally and during stimulation with pentagastrin (6 μg/kg body weight subcutaneously) at the end of weeks 1 and 3. Pentagastrin stimulation mimics food stimulation. The mucus content in gastric juice was assessed gravimetrically. The mucin content was measured after its purification using ultracentrifugation. The viscosity of the gastric secretion was measured using a digital viscometer. In comparison with placebo, the volume of gastric secretion in patients with CC during administration of lubiprostone increased significantly by 50% (86.3 vs. 57.5 ml/h) (P<0.001) in basal conditions and increased by 25% (210.0 vs. 167.6 ml/h) (P=0.024) during stimulation with pentagastrin. The rate of gastric mucus secretion during therapy with lubiprostone was 91% higher (257.3 vs. 135 mg/h) (P=0.001) in basal conditions and 28% higher (348.1 vs. 270.8 mg/h) (NS) in stimulated conditions, although the latter was not statistically significant. The rate of gastric mucin secretion during lubiprostone therapy was 85% higher (98.4 vs. 65.5 mg/h) (P=0.011) in basal conditions and 38% (98.3 vs. 71.7 mg/h) (NS) higher in stimulated conditions. In basal conditions, the viscosity of gastric secretion during administration of lubiprostone increased by 240% at the lowest (P<0.001) and by 106% at the highest shear rate (P<0.001). In stimulated conditions, it increased by 226% (P<0.01) at the lowest shear rate and by 67% (P<0.01) at the highest shear rate. The significantly higher content of gastric mucus and mucin during therapy in basal conditions with lubiprostone in patients with CC suggests and supports the potentially leading role of lubiprostone and ClC-2 stimulation in their secretion. This increased stimulation results in profoundly increased viscosity, which in turn facilitates and/or accelerates the transit and evacuation of non-digestible food components. Although increases in mucus and mucin were observed in stimulated conditions, neither increase was statistically significant. Based on this experiment, we hypothesize that, in CC patients, the significantly increased rate of mucus and its major component, mucin secretion, during lubiprostone administration may partially explain its clinical effectiveness and also have additional clinically important effects. We propose that since the increased mucus production enhances the protective quality of the mucosal barrier, it also boosts its potential to withstand luminal aggressive components such as acid/pepsin duet, Helicobacter pylori and/or nonsteroidal anti-inflammatory drugs/aspirin, or a combination of all. Further trials are needed to test this hypothesis. As this was crossover clinical trial, the patients serve as their own controls. No interaction was found with body mass index (BMI) and treatment. The observed relationships of BMI and mucus and mucin secretions and gastric juice volume are important considerations in the design of future trials, particularly if a crossover design is not used.

Stimulation of Mucin, Mucus, and Viscosity during Lubiprostone in Patients with Chronic Constipation may Potentially Lead to Increase of Lubrication

PubMed Central

Majewski, Marek; Sarosiek, Irene; Wallner, Grzegorz; Edlavitch, Stanley A; Sarosiek, Jerzy

2014-01-01

Objectives: The purpose of this clinical trial was to explore whether lubiprostone increases the rate of mucus and mucin secretion and its viscosity in chronic constipation (CC) patients. The secretion of chloride (CS) into the gastrointestinal tract lumen is pivotal in the body's ability to process non-digestible food components. CS sets the optimal rate of hydration for non-digestible food components, their fluidity, and their adequate propulsion along the alimentary tract. Chloride is also instrumental in the secretion of alimentary tract mucus, and the formation of a gel-like, viscous mucus-buffer layer. This layer acts as the first line and vanguard of the mucosal barrier. This barrier is essential in mucosal lubrication and protection. Lubiprostone, a novel chloride channel stimulator ClC-2, is currently approved for the treatment of CC. Its impact on mucus, mucus secretion, and viscosity is not established. Methods: A double-blind, crossover trial was approved by the IRBs at the Kansas University Medical Center (Kansas City, KS) (study site) and at the Texas Tech University HSC (El Paso, TX) (analysis site). The study included 20 patients (17 females (F); mean age: 37 years) with symptoms of CC diagnosed according to the Rome III criteria. Patients were randomized to 1 week of therapy with lubiprostone or placebo followed by a 1 week washout and 1 week of the alternative therapy. Gastric juice was collected basally and during stimulation with pentagastrin (6 μg/kg body weight subcutaneously) at the end of weeks 1 and 3. Pentagastrin stimulation mimics food stimulation. The mucus content in gastric juice was assessed gravimetrically. The mucin content was measured after its purification using ultracentrifugation. The viscosity of the gastric secretion was measured using a digital viscometer. Results: In comparison with placebo, the volume of gastric secretion in patients with CC during administration of lubiprostone increased significantly by 50% (86.3 vs. 57.5 ml/h) (P<0.001) in basal conditions and increased by 25% (210.0 vs. 167.6 ml/h) (P=0.024) during stimulation with pentagastrin. The rate of gastric mucus secretion during therapy with lubiprostone was 91% higher (257.3 vs. 135 mg/h) (P=0.001) in basal conditions and 28% higher (348.1 vs. 270.8 mg/h) (NS) in stimulated conditions, although the latter was not statistically significant. The rate of gastric mucin secretion during lubiprostone therapy was 85% higher (98.4 vs. 65.5 mg/h) (P=0.011) in basal conditions and 38% (98.3 vs. 71.7 mg/h) (NS) higher in stimulated conditions. In basal conditions, the viscosity of gastric secretion during administration of lubiprostone increased by 240% at the lowest (P<0.001) and by 106% at the highest shear rate (P<0.001). In stimulated conditions, it increased by 226% (P<0.01) at the lowest shear rate and by 67% (P<0.01) at the highest shear rate. Conclusions: The significantly higher content of gastric mucus and mucin during therapy in basal conditions with lubiprostone in patients with CC suggests and supports the potentially leading role of lubiprostone and ClC-2 stimulation in their secretion. This increased stimulation results in profoundly increased viscosity, which in turn facilitates and/or accelerates the transit and evacuation of non-digestible food components. Although increases in mucus and mucin were observed in stimulated conditions, neither increase was statistically significant. Based on this experiment, we hypothesize that, in CC patients, the significantly increased rate of mucus and its major component, mucin secretion, during lubiprostone administration may partially explain its clinical effectiveness and also have additional clinically important effects. We propose that since the increased mucus production enhances the protective quality of the mucosal barrier, it also boosts its potential to withstand luminal aggressive components such as acid/pepsin duet, Helicobacter pylori and/or nonsteroidal anti-inflammatory drugs/aspirin, or a combination of all. Further trials are needed to test this hypothesis. As this was crossover clinical trial, the patients serve as their own controls. No interaction was found with body mass index (BMI) and treatment. The observed relationships of BMI and mucus and mucin secretions and gastric juice volume are important considerations in the design of future trials, particularly if a crossover design is not used. PMID:25521039

Calcitonin secretion in congenital nongoitrous cretinism.

PubMed

Carey, D E; Jones, K L; Parthemore, J G; Deftos, L J

1980-04-01

Plasma calcitonin (CT) was measured in the basal state and/or during provocative tests of hormone secretion in 11 children with congenital non-goitrous cretinism (CNC), in 1 girl with a lingual thyroid, and in 11 normal children. Basal and stimulated CT concentrations were significantly lower in the patients with CNC than in the normal subjects. Mean basal CT (+/- SE) was 41 +/- 4 pg/ml in the normal children, 24 +/- 3 pg/ml in the children with CNC, and 20 +/- 2 pg/ml in the patient with the lingual thyroid. The mean incremental CT responses to calcium infusion were 7.0 +/- 2 pg/ml in the children with CNC, 6.0 pg/ml in the patient with the lingual thyroid, and 146 +/- 47 pg/ml in the normal children. The children with CNC also demonstrated a significant delay in the return of the total serum calcium to basal level after the calcium infusion. The mean incremental CT response after infusion of pentagastrin was 7.6 +/- 2 pg/ml in the children with CNC, 10.0 pg/ml in the child with the lingual thyroid, and 34.4 +/- 11 pg/ml in the normal children. These data indicate that CT deficiency is present in children with CNC and suggest that the deficiency is a consequence of the defective embryologic development of the thyroid gland.

Substance P in the dorsal vagal complex inhibits medullary TRH-induced gastric acid secretion in rats.

PubMed

Yang, H; Taché, Y

1997-05-01

Neurons that contain substance P (SP) and thyrotropin-releasing hormone (TRH) in medullary midline raphe nuclei project to the dorsal vagal complex (DVC). The modulatory role of SP on basal gastric acid secretion (GAS) and TRH on DVC-induced stimulation of GAS was studied in urethan-anesthetized rats. The stable SP agonist, DiMe-C7 ([pGlu5, MePhe8, MeGly9]SP5-11, 50 and 100 pmol), injected unilaterally into the DVC reduced the GAS response (47 +/- 12 mumol/60 min) to coinjected TRH analog, RX 77368 (25 pmol), by 53% and 85%, respectively, whereas DiMe-C7 (100 pmol) alone had no effect on basal and pentagastrin-stimulated GAS. DiMe-C7 (100 pmol/site) inhibited the GAS response to kainic acid injected into the raphe pallidus (Rpa) when it was injected bilaterally into the DVC but not the hypoglossal nuclei. The SP nourokinin-1-receptor antagonist, CP-96,345, injected bilaterally into the DVC (1 nmol/ site) increased basal GAS (33 +/- 8 mumol/90 min) and potentiated the GAS response to kainic acid injected into the Rpa by 40%. These results suggest that SP acts on neurokinin-1 receptors in the DVC to reduce medullary TRH-induced stimulation of GAS in rats.

JB-9322, a new selective histamine H2-receptor antagonist with potent gastric mucosal protective properties.

PubMed

Palacios, B; Montero, M J; Sevilla, M A; Román, L S

1995-05-01

1. JB-9322 is a selective histamine H2-receptor antagonist with gastric antisecretory activity and mucosal protective properties. 2. The affinity of JB-9322 for the guinea-pig atria histamine H2-receptor was approximately 2 times greater than that of ranitidine. 3. In vivo, the ID50 value for the inhibition of gastric acid secretion in pylorus-ligated rats was 5.28 mg kg-1 intraperitoneally. JB-9322 also dose-dependently inhibited gastric juice volume and pepsin secretion. In gastric lumen-perfused rats, intravenous injection of JB-9322 dose-dependently reduced histamine-, pentagastrin- and carbachol-stimulated gastric acid secretion. 4. JB-9322 showed antiulcer activity against aspirin and indomethacin-induced gastric lesions and was more potent than ranitidine. 5. JB-9322 effectively inhibited macroscopic gastric haemorrhagic lesions induced by ethanol. Intraperitoneal injection was effective in preventing the lesions as well as oral treatment. The oral ID50 value for these lesions was 1.33 mg kg-1. By contrast, ranitidine (50 mg kg-1) failed to reduce these lesions. In addition, the protective effect of JB-9322 was independent of prostaglandin synthesis. 6. These results indicate that JB-9322 is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity.

Simultaneous measurements of gastric motility and acid-bicarbonate secretions in the anaesthetized cat.

PubMed

Fändriks, L; Stage, L

1986-12-01

Chloralosed cats were acutely vagotomized, their splanchnic nerves cut and the adrenal glands ligated. The gastric lumen was perfused with isotonic NaCl and gastric motility was monitored as changes in hydrostatic pressure within the perfusion circuit. Gastric secretion of H+ and HCO3- were calculated from continuous measurements of pH and PCO2. Methodological tests ex vivo showed good accuracy of the estimations. Recovery of H+ after HCl instillation into the stomach in vivo was almost complete, while HCO3- recovery after NaHCO3 instillations was 85-95%. Pentagastrin (10 micrograms kg-1 h-1 i.v.) stimulated gastric contractile activity and increased gastric H+ secretion 30-fold, while HCO3- secretion decreased somewhat. Carbachol (4 micrograms kg-1 h-1) induced gastric contractions and increased H+ secretion by 400% and HCO3- output by 100-130%. Electrical stimulation of the cut vagal nerves (10 Hz for 10 min) induced well known gastric motor responses and increased gastric H+ secretion 20-fold preceded by a transient doubling of HCO3- secretion. Omeprazole, a selective inhibitor of gastric H+ secretion, decreased the vagally induced H+ secretion, while recorded gastric HCO3- secretion was clearly enhanced. In conclusion, the technique permits simultaneous recordings of rapid alterations of gastric motility and H+ and HCO3- secretions. However, HCO3- secretion was modestly underestimated, probably due to mucosal CO2 absorption.

Pharmacology of JB-9315, a new selective histamine H2-receptor antagonist.

PubMed

Palacios, B; Montero, M J; Sevilla, M A; San Román, L

1998-02-01

1. The histamine H2-receptor antagonistic activity and antisecretory and antiulcer effects of JB-9315 were studied in comparison with the standard H2 blocker ranitidine. 2. In vitro, JB-9315 is a competitive antagonist of histamine H2 receptors in the isolated, spontaneously beating guinea-pig right atrium, with a pA2 value of 7.30 relative to a value of 7.36 for ranitidine. JB-9315 was specific for the histamine H2 receptor because, at high concentration, it did not affect histamine- or acetylcholine-induced contractions in guinea-pig isolated ileum or rat isolated duodenum, respectively. 3. JB-9315 dose dependently inhibited histamine-, pentagastrin- or carbachol-stimulated acid secretion and basal secretion in the perfused stomach preparation of the anesthetized rat. In the pylorus-ligated rat after intraperitoneal administration, total acid output over 4 h was inhibited by JB-9315 with an ID50 of 32.8 mg/kg, confirming its H2-receptor antagonist properties. 4. JB-9315 showed antiulcer activity against cold stress plus indomethacin-induced lesions with an ID50 of 6.8 mg/kg. 5. JB-9315, 50 and 100 mg/kg, inhibited macroscopic gastric hemorrhagic lesions induced by ethanol. In contrast, ranitidine (50 mg/kg) failed to reduce these lesions. 6. These results indicate that JB-9315 is a new antiulcer drug that exerts a cytoprotective effect in addition to its gastric antisecretory activity.

The Daily Consumption of Cola Can Determine Hypocalcemia: A Case Report of Postsurgical Hypoparathyroidism-Related Hypocalcemia Refractory to Supplemental Therapy with High Doses of Oral Calcium.

PubMed

Guarnotta, Valentina; Riela, Serena; Massaro, Marina; Bonventre, Sebastiano; Inviati, Angela; Ciresi, Alessandro; Pizzolanti, Giuseppe; Benvenga, Salvatore; Giordano, Carla

2017-01-01

The consumption of soft drinks is a crucial factor in determining persistent hypocalcemia. The aim of the study is to evaluate the biochemical mechanisms inducing hypocalcemia in a female patient with usual high consumption of cola drink and persistent hypocalcemia, who failed to respond to high doses of calcium and calcitriol supplementation. At baseline and after pentagastrin injection, gastric secretion (Gs) and duodenal secretion (Ds) samples were collected and calcium and total phosphorus (P tot ) concentrations were evaluated. At the same time, blood calcium, P tot , sodium, potassium, chloride, magnesium concentrations, and vitamin D were sampled. After intake of cola (1 L) over 180 min, Gs and Ds and blood were collected and characterized in order to analyze the amount of calcium and P tot or sodium, potassium, magnesium, and chloride ions, respectively. A strong pH decrease was observed after cola intake with an increase in phosphorus concentration. Consequently, a decrease in calcium concentration in Gs and Ds was observed. A decrease in calcium concentration was also observed in blood. In conclusion, we confirm that in patients with postsurgical hypoparathyroidism, the intake of large amounts of cola containing high amounts of phosphoric acid reduces calcium absorption efficiency despite the high doses of calcium therapy.

The gastric mucosal barrier.

PubMed

Clamp, J R; Ene, D

1989-01-01

The gastric mucosal barrier is a complex system made up of submucosal, epithelial and mucus elements. The mucus gel layer is a thick tenacious organized layer adherent to the epithelium. Despite these properties it is composed of more than 95% water, the organization being provided by long interacting glycoprotein molecules (mucus glycoprotein or mucin). These molecules are largely made up of carbohydrate which is present in large numbers of relatively small oligosaccharide units packed around the polypeptide core. This structure provides clues to the nature of the protection afforded by the mucus layer. For example, it is relatively resistant to proteolysis in the gastrointestinal tract; it retains water in an unstirred layer; the tangled glycoproteins exclude large molecules and the carbohydrate of the oligosaccharide units mirror that at the surface of the epithelial cell. Few biochemical studies have been carried out on the effect of ulcer-healing drugs on gastric mucus. Normal subjects were, therefore, given two weeks treatment with cimetidine, carbenoxolone or misoprostol and the secretions aspirated from the unstimulated and pentagastrin-stimulated stomach. The volume of secretion and weight and carbohydrate content of non-diffusable glycoconjugates were determined for each specimen, together with the proportion of high molecular mass mucin and qualitative and quantitative analyses of the glycopolypeptide. There were no significant differences between the results for each drug or without drug. This may be because normal subjects were studied who already have an effective mucosal barrier. In addition, it is likely that the process of mucus biosynthesis and secretion in a healthy individual is relatively resistant to the action of ulcer healing drugs.

Role of nitrite, urate and pepsin in the gastroprotective effects of saliva

PubMed Central

Rocha, Bárbara S.; Lundberg, Jon O; Radi, Rafael; Laranjinha, João

2016-01-01

Dietary nitrate is now recognized as an alternative substrate for nitric oxide (•NO) production in the gut. This novel pathway implies the sequential reduction of nitrate to nitrite, •NO and other bioactive nitrogen oxides but the physiological relevance of these oxidants has remained elusive. We have previously shown that dietary nitrite fuels an hitherto unrecognized nitrating pathway at acidic gastric pH, through which pepsinogen is nitrated in the gastric mucosa, yielding a less active form of pepsin in vitro. Here, we demonstrate that pepsin is nitrated in vivo and explore the functional impact of protein nitration by means of peptic ulcer development. Upon administration of pentagastrin and human nitrite-rich saliva or sodium nitrite to rats, nitrated pepsin was detected in the animal's stomach by immunoprecipitation. •NO was measured in the gastric headspace before and after nitrite instillation by chemiluminescence. At the end of each procedure, the stomach's lesions, ranging from gastric erosions to haemorrhagic ulcers, were scored. Nitrite increased gastric •NO by 200-fold (p<0.05) and nitrated pepsin was detected both in the gastric juice and the mucosa (p<0.05). Exogenous urate, a scavenger of nitrogen dioxide radical, blunted •NO detection and inhibited pepsin nitration, suggesting an underlining free radical-dependent mechanism for nitration. Functionally, pepsin nitration prevented the development of gastric ulcers, as the lesions were only apparent when pepsin nitration was inhibited by urate. In sum, this work unravels a novel dietary-dependent nitrating pathway in which pepsin is nitrated and inactivated in the stomach, preventing the progression of gastric ulcers. PMID:27156250

Results of early thyroidectomy for medullary thyroid carcinoma in children with multiple endocrine neoplasia type 2.

PubMed

Telander, R L; Zimmerman, D; van Heerden, J A; Sizemore, G W

1986-12-01

Children with multiple endocrine neoplasia type 2 (MEN2) often develop medullary carcinoma of the thyroid (MCT) or its precursor, C-cell hyperplasia. Survival results are improved if malignancy is diagnosed early from the results of plasma immunoreactive calcitonin (iCT) measurement. The effect of early detection and thyroidectomy in children with MEN2 syndrome was determined by reviewing the experience between 1975 and 1985. Seventeen children with MEN2 who were 12 years old or younger underwent a total thyroidectomy for MCT or C-cell hyperplasia. iCT was measured in all patients preoperatively and postoperatively. Of the 17 children, 14 (82%) had MEN2a and 3 (18%) had MEN2b. There were 14 (82%) female and three (18%) male patients; their mean age was 6.97 years (range 1.5 to 12 years). In all patients, the diagnosis of MCT was made from initial elevated levels of iCT after stimulation with pentagastrin. Three patients had clinical evidence of disease preoperatively. All patients underwent a total thyroidectomy and lymph nodes were removed from the central zone; a neck dissection was performed in the three with clinically obvious disease. MCT with C-cell hyperplasia was found in 11 children and C-cell hyperplasia alone in six. Of the 11 with carcinoma, eight had bilateral disease and three unilateral. Six children had bilateral C-cell hyperplasia. All 17 children were alive and feeling well at the time of this report; however, three had evidence of metastatic disease according to iCT measurements. None of the children had recurrent nerve injuries; one had evidence of hypoparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of gastric acid and mucus secretion level with low-dose aspirin-induced gastropathy.

PubMed

Iijima, Katsunori; Ara, Nobuyuki; Abe, Yasuhiko; Koike, Tomoyuki; Iwai, Wataru; Iwabuchi, Toshimitsu; Ichikawa, Takafumi; Kamata, Yayoi; Ishihara, Kazuhiko; Shimosegawa, Tooru

2012-02-01

Low-dose aspirin is known to cause upper gastrointestinal complications. The mechanism by which the aspirin disrupts gastric mucosal integrity remains to be clarified. In this study we investigated the temporal association of gastric secretory parameters (acid and mucus) with aspirin-induced gastropathy. In 42 long-term low-dose aspirin-takers and the same number of sex- and age-matched controls, pentagastrin-stimulated gastric juice was collected for 10 min during endoscopic examination. The collected gastric juice was divided and half was submitted to analysis for gastric acid (mEq/10 min) and the other half was analyzed for mucin (mg hexose/10 min) output. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score, and a score of more than 4 was defined as the presence of severe gastropathy. While gastric acid secretion did not differ significantly between aspirin-takers and controls, gastric mucus secretion, in terms of mucin output, was significantly increased in aspirin-takers compared to controls (4.1 (SD 4.8) vs. 2.3 (1.4) mg hexose/10 min, P < 0.05). Consequently, the acid/mucin ratio was significantly decreased in aspirin-takers compared to controls (1.2 (1.0) vs. 1.7 (1.4), P < 0.05). In the subanalysis of 25 aspirin-takers without severe gastropathy, gastric mucus secretion was increased and the acid/mucus ratio was decreased compared with controls, but there was no such association in the remaining 17 aspirin-takers with severe gastropathy. Overall, gastric mucus secretion is increased in aspirin-takers, suggesting a functional adaptive response to long-term administration of the drug. However, it is possible that the adaptive response is impaired in some aspirin takers, who might be susceptible to severe upper gastrointestinal complication.

Binding and degradation of 125I-gastrin by plasma membranes from homogenized rat gastric mucosa.

PubMed

Kleveland, P M; Waldum, H L

1986-06-01

Binding of 125I-gastrin to the 270-30,000 g fraction from homogenized rat oxyntic mucosa was studied. 'Specific' binding was calculated by subtracting the binding at excess cold gastrin from the binding with labelled gastrin (250 pM) only. At 30 degrees C specific binding rose rapidly to a short-lived maximum before falling gradually, whereas at 15 degrees C and 0 degree C specific binding rose gradually to a higher plateau level. The reduced binding at 30 degrees C could be caused by degradation of either the tracer or the binding site or by a combination of these two events. Degradation of 125I-gastrin was evaluated by trichloroacetic acid (TCA) precipitation, fast protein liquid chromatography, and binding to a gastrin antibody (immunoreactivity). The effect of incubation on the binding site was evaluated by preincubation of the homogenate fraction before adding gastrin. In separate studies, the proteolytic activity of the homogenate fraction was studied by TCA precipitation of radioactive casein. Different enzyme inhibitors tested were virtually ineffective in preventing gastrin and casein degradation. Only lowering the incubation temperature to 15 degrees C or lower could prevent this degradation. The reduced and transient binding of 125I-gastrin at 30 degrees C most probably reflects tracer degradation. Accordingly, the gastrin binding experiments were performed at 15 degrees C. Only homogenates from the oxyntic area of the stomach bound 125I-gastrin specifically and with a Kd of 0.8 nM (Scatchard analysis). However, micromolar concentrations of unlabelled gastrin were required to inhibit half maximal binding of the tracer. The tracer binding was unaffected by secretin, slightly reduced by a CCK-9 analogue, and more markedly reduced by pentagastrin.

A newly detected mutation of the RET protooncogene in exon 8 as a cause of multiple endocrine neoplasia type 2A.

PubMed

Bethanis, Sotirios; Koutsodontis, George; Palouka, Theodosia; Avgoustis, Christos; Yannoukakos, Drakoulis; Bei, Thalia; Papadopoulos, Savas; Linos, Dimitrios; Tsagarakis, Stylianos

2007-01-01

Multiple endocrine neoplasia type 2A (MEN2A) is a syndrome of familial neoplasias characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia of the parathyroid glands. RET protooncogene mutations are responsible for MEN 2A. Mutations in exons 10 or 11 have been identified in more than 96% of patients with MEN 2A. We herein report for the first time a patient with MEN 2A harboring a mutation (Gly(533)Cys) in exon 8. A 66-year old male patient was referred to our department for bilateral adrenal nodules. The patient's family history was remarkable in that his mother had pheochromocytoma. Biochemical evaluation and findings of the magnetic resonance imaging of the adrenals were compatible with the diagnosis of bilateral pheochromocytomas. The patient underwent laparoscopic bilateral adrenalectomy and histological examination confirmed the preoperative diagnosis of pheochromocytoma. Absence of phenotypic characteristics of VHL or NF1 and elevated calcitonin levels both basal and post pentagastrin stimulation, raised the possibility of MEN 2A syndrome. Total thyroidectomy was performed and histological examination showed the presence of MTC. Direct sequencing of exon 8 from the patient's genomic DNA revealed the mutation c.1,597G-->T (Gly533Cys). Although this missense point mutation has been associated with familial MTC (FMTC), to the best of our knowledge mutations in exon 8 have not previously been identified in patients with MEN 2A. In conclusion, in patients with clinical suspicion of MEN 2A syndrome, analysis of RET exon 8 should be considered when the routine evaluation of MEN 2A-associated mutations is negative. Furthermore, patients with FMTC and exon 8 mutations should also be screened for pheochromocytoma.

Acid-gastric antisecretory effect of the ethanolic extract from Arctium lappa L. root: role of H+, K+-ATPase, Ca2+ influx and the cholinergic pathway.

PubMed

da Silva, Luisa Mota; Burci, Ligia de Moura; Crestani, Sandra; de Souza, Priscila; da Silva, Rita de Cássia Melo Vilhena de Andrade Fonseca; Dartora, Nessana; de Souza, Lauro Mera; Cipriani, Thales Ricardo; da Silva-Santos, José Eduardo; André, Eunice; Werner, Maria Fernanda de Paula

2018-04-01

Arctium lappa L., popularly known as burdock, is a medicinal plant used worldwide. The antiulcer and gastric-acid antisecretory effects of ethanolic extract from roots of Arctium lappa (EET) were already demonstrated. However, the mechanism by which the extract reduces the gastric acid secretion remains unclear. Therefore, this study was designed to evaluate the antisecretory mode of action of EET. The effects of EET on H + , K + -ATPase activity were verified in vitro, whereas the effects of the extract on cholinergic-, histaminergic- or gastrinergic-acid gastric stimulation were assessed in vivo on stimulated pylorus ligated rats. Moreover, ex vivo contractility studies on gastric muscle strips from rats were also employed. The incubation with EET (1000 µg/ml) partially inhibited H + , K + -ATPase activity, and the intraduodenal administration of EET (10 mg/kg) decreased the volume and acidity of gastric secretion stimulated by bethanechol, histamine, and pentagastrin. EET (100-1000 µg/ml) did not alter the gastric relaxation induced by histamine but decreased acetylcholine-induced contraction in gastric fundus strips. Interestingly, EET also reduced the increase in the gastric muscle tone induced by 40 mM KCl depolarizing solution, as well as the maximum contractile responses evoked by CaCl 2 in Ca 2+ -free depolarizing solution, without impairing the effect of acetylcholine on fundus strips maintained in Ca 2+ -free nutritive solution. Our results reinforce the gastric antisecretory properties of preparations obtained from Arctium lappa, and indicate that the mechanisms involved in EET antisecretory effects include a moderate reduction of the H + , K + -ATPase activity associated with inhibitory effects on calcium influx and of cholinergic pathways in the stomach muscle.

The effects of chronic consumption of heroin on basal and vagal electrical-stimulated gastric acid and pepsin secretion in rat.

PubMed

Rafsanjani, Fatemeh N; Maghouli, Fatemeh; Vahedian, Jalal; Esmaeili, Farzaneh

2004-10-01

Addiction to opium and heroin is not only an important social and individual problem in the world but it also affects the human physiology and multiple systems. The aim of this study is to determine the effects of chronic heroin consumption on basal and vagus electrical-stimulated total gastric acid and pepsin secretion in rats. The study was carried out in the Department of Physiology, Kerman University of Medical Sciences, Iran from August 2002 to June 2003. Both male and female rats weighing 200-250 g were used. Rats received daily doses of heroin intraperitoneally starting from 0.2 mg/kg to 0.1 mg/kg/day up to the maintenance level of 0.7 mg/kg and continued until day 12. After anesthesia, tracheotomy and laparotomy, gastric effluents were collected by washout technique with a 15 minutes interval. The total titrable acid was measured by manual titrator, and the total pepsin content was measured by Anson's method. Vagal electrical stimulation was used to stimulate the secretion of acid and pepsin. Heroin results in a significant decrease in total basal acid and pepsin secretions (4.10 +/- 0.18 mmol/15 minutes versus 2.40 +/- 0.16 mmol/15 minutes for acid, p<0.01, and 3.63 +/- 0.18 mg/15 minutes versus 3.11+/- 0.18 mg/15 minutes for pepsin, p<0.05). But, it does not produce any significant changes in acid and pepsin secretions in vagotomized condition. Heroin also causes a significant decrease in vagal-electrically stimulated acid and pepsin secretions (14.70 +/- 0.54 mmol/15 minutes versus 4.30 +/- 0.21 mmol/15 minutes for acid, p<0.01, and 3.92 +/-0.16 mg/15 minutes versus 3.37+/- 0.16 mg/15 minutes for pepsin, p<0.05). Heroin consumption decreases the total gastric basal and vagus stimulation of acid and pepsin secretion, but not in vagotomized condition. Heroin may decrease acid secretion by inhibiting vagal release of acetylcholine within the gastric wall. Other probable mechanisms include: presynaptic inhibition of acetylcholine release or depressing the vagal center, inhibition of pentagastrin induced acid secretion, inhibitory effects via central mechanisms, probably mediated by the opiate receptors. Further studies are needed to recognize the actual mechanism.

[Neurobiology and pharmacotherapy of social phobia].

PubMed

Aouizerate, B; Martin-Guehl, C; Tignol, J

2004-01-01

Social phobia (also known as social anxiety disorder) is still not clearly understood. It was not established as an authentic psychiatric entity until the diagnostic nomenclature of the American Psychiatric Association DSM III in 1980. In recent years, increasing attention among researchers has contributed to provide important information about the genetic, familial and temperamental bases of social phobia and its neurochemical, neuroendocrinological and neuroanatomical substrates, which remain to be further investigated. Up to date, there have been several findings about the possible influence of variables, including particularly genetic, socio-familial and early temperamental (eg behavioral inhibition) factors that represent risk for the later development of social phobia. Clinical neurobiological studies, based on the use of exogenous compounds such as lactate, CO2, caffeine, epinephrine, flumazenil or cholecystokinin/pentagastrin to reproduce naturally occurring phobic anxiety, have shown that patients with social phobia appear to exhibit an intermediate sensitivity between patients with panic disorder and control subjects. No difference in the rate of panic attacks in response to lactate, low concentrations of CO2 (5%), epinephrine or flumazenil was observed between patients with social phobia and normal healthy subjects, both being less reactive compared to patients with panic disorder. However, patients with social phobia had similar anxiety reactions to high concentrations of CO2 (35%), caffeine or cholecystokinin/pentagastrin than those seen in patients with panic disorder, both being more intensive than in controls. Several lines of evidence suggest specific neurotransmitter system alterations in social phobia, especially with regard to the serotoninergic, noradrenergic and dopaminergic systems. Although no abnormality in platelet serotonin transporter density has been found, patients with social phobia appear to show an enhanced sensitivity of both post-synaptic 5HT1A and 5HT2 serotonin receptor subtypes, as reflected by increased anxiety and hormonal responses to serotoninergic probes. Platelet 5HT2 receptor density has also been reported to be positively correlated to symptom severity in patients with social phobia. During anticipation of public speaking, heart rate was elevated in patients with social phobia compared to controls. Norepinephrine response to the orthostatic challenge test or to the Valsalva maneuver was also greater in patients with social phobia. While normal beta-adrenergic receptor number was observed in lymphocytes, a blunted response of growth hormone to clonidine, an a2-adrenergic agonist, was reported. This suggests reduced post-synaptic a2-adrenergic receptor functioning related to norepinephrine overactivity in social phobia. Decreased cerebrospinal fluid levels of the dopamine metabolite homovanillic acid have also been observed. There are relatively few reports of involvement of the adrenal and thyroid functions in social phobia, and all that has been noted is that patients with social phobia show an exaggerated adrenocortical response to a psychological stressor. Recent advances in neuro-imaging have contributed to find low striatal dopamine D2 receptor binding or low dopamine transporter site density in patients with social phobia. They have also demonstrated the involvement of the cortico-limbic pathways, including the prefrontal cortex, hippocampus and amygdala, which show an increased activity in different experimental conditions. These brain regions have extensively been reported to play an important role in the cognitive appraisal in determining the significance of environmental stimuli, in the emotional and mnemonic integration of information, and in the expression of contextual fear-conditioned behaviors, which might be disrupted in the light of the phenomelogical aspects of social phobia. A substantial body of literature based on case reports, open and placebo-controlled trials, has now clearly examined the efficacy of major classes of psychotropic agents including monoamine oxidase inhibitors, beta-blockers, selective serotonin reuptake inhibitors and benzodiazepines in social phobia. Until recently, irreversible non-selective monoamine oxidase inhibitors, of which phenelzine was the most extensively evaluated, were considered as the most efficacious treatment in reducing the symptomatology associated with social phobia in 50-70% of cases after 4 to 6 weeks. However, side effects and dietary restrictions limit their use. This led to the development of reversible inhibitors of monoamine oxidase A, for which careful dietary monitoring is not required. Moclobemide has been the most widely studied but produced unconvincingly therapeutic effects on social phobic symptoms. To date, selective serotonin reuptake inhibitors may be considered as a reasonable first-line pharmacotherapy for social phobia. There is growing evidence for the efficacy of the selective serotonin reuptake inhibitors fluvoxamine, fluoxetine, citalopram, paroxetine and sertraline. They have beneficial effects with response rates ranging from 50 to 80% in social phobia. It has been recommended that the treatment period should be extended at least 6 months beyond the early improvement achieved within the first 4 to 6 weeks. The overall advantages include tolerability with a low risk of adverse events. The benzodiazepines clonazepam and alprazolam have also been proposed for the treatment of social phobia. Symptomatic relief occurred in 40 to 80% of the cases with a relatively rapid onset of action within the first two weeks. Untoward effects, discontinuation-related withdrawal symptoms and abuse or dependence liability constitute major concerns about the use of benzodiazepines, so they should be reserved for cases unresponsive to the safer medications cited above. Beta-blockers such as atenolol and propanolol have commonly been employed in performance anxiety, decreasing autonomic symptoms (eg, tachycardia, sweating and dry mouth). However, they are not effective in the generalized form of social phobia. Other pharmacologic alternatives seem helpful for the management of social phobia, including venlafaxine, gabapentin, bupropion, nefazodone or augmentation with buspirone. Preliminary studies point to promising effects of these agents. Larger controlled clinical trials are now needed to confirm their potential role in the treatment of social phobia.

Regulatory effect and mechanism of gastrin and its antagonists on colorectal carcinoma

PubMed Central

He, Shuang-Wu; Shen, Kang-Qiang; He, Yu-Jun; Xie, Bin; Zhao, Yan-Ming

1999-01-01

AIM: To explore the effect and mechanism of gastrin and its an tagonists proglumide and somatostatin on colorectal carcinoma and their clinical significance. METHODS: A model of transplanted human colonic carcinoma was established from SW480 cell line in gymnomouse body. The volume and weight of transplanted carcinoma was observed under the effect of pentagatrin (PG), proglumide (PGL) and octapeptide somotostatin (SMS201-995, SMS). The cAMP content of carcinoma cell was determined by radioimmunoassay and the DNA, protein content and cell cycle were determined by flow-cytometry. The amount of viable cells was determined by MTT colorimetric analysis, IP3 content was determined by radioimmuno assay, Ca2+ concentration in cell by fluorometry and PKC activity by isotopic enzymolysis. The expression of gastrin, c-myc, c-fos and rasP21 in 48 case s of colorectal carcinoma tissue was detected by the immuno-cytochemistry SP method. Argyrophilia nucleolar organizer regions was determined with argyrophilia stain. RESULTS: The volume, weight, cAMP, DNA and protein content in carcinoma cell, cell amount and proliferation index of S and G2M phase in PG group were all significantly higher than those of control group. When PG was at the concentration of 25 mg/L, the amount of viable cells, IP3 content and Ca2+ concentration in cell and membrane PKC activity in PG group were significantly higher than those in control group; when PGL was at a concentration of 32 mg/L, they dropped to the lowest level in PG (25 mg/L) + PGL group, but without significant difference from the control group. The positive expression rate of gastrin, c-myc, c-fos and rasP21 in carcinoma tissue was 39.6%, 54.2%, 47.9% and 54.2% respectively and significantly higher than that in mucosa 3 cm and 6 cm adjacent to carcinoma tissue and normal colorectal mucosa. The positive expression rate of gastrin of highly-differentiated adenocarcinoma group was significantly higher than that of poorly-differentiated and mucinous adenoc arcinoma groups. The AgNORs count of carcinoma tissue was significantly higher than that in mucosa 3 cm and 6 cm adjacent to carcinoma tissue and norm al colorectal mucosa; and the positive expression of c-myc and c-fos and the A gNORs count in gastrin-positive group was significantly higher than those in gastrin-negative group. CONCLUSION: Pentagastrin has a promoting effect on the growth of transplanted human colonic carcinoma from SW480 cell line. PGL has no obvious effect on the growth of human colonic carcinoma SW480 cell line, but could inhibit the growth promoting effect of PG on transplanted carcinoma. Somatostatin can not only inhibit the growth of transplanted human colonic carcinoma from SW480 cell line directly but also depress the growth-promoting effect of gastrin on the transplanted carcinoma. Some colorectal carcinoma cells can produce and secrete gastrin through autocrine, highly-differentiated adenocarcinoma express the highest level gastrin. Endogenous gastrin can stimulate the cell division and proliferation of carcinoma cell and promote the growth of colorectal carcinoma regulating the expression of oncogene c-myc, c-fos. Our study has provided experimental basis for the adjuvant treatment using gastrin antagonist such as PGL, so matostatin of patients with colorectal carcinoma. PMID:11819478

Cholecystokinin in the control of gastric acid and plasma gastrin and somatostatin secretion in healthy subjects and duodenal ulcer patients before and after eradication of Helicobacter pylori.

PubMed

Konturek, J W

1994-12-01

Exogenous cholecystokinin (CCK) is known to effect gastric secretory and motor functions but its physiological role in the control of these functions in healthy subjects and duodenal ulcer (DU) patients is unknown. In this study involving four series of young healthy normal and DU subjects, the gastric secretory tests were performed under basal conditions and following stimulation by modified sham-feeding (MSF), i.v. infusion of caerulein, gastrin releasing peptide (GRP) or pentagastrin (p-gastrin) (series A), after 500 ml of standard meal without or with addition of 15% soybean oil (series B) or acidification of meal to pH 2.5 (series C), and finally after eradication of Helicobacter pylori (HP) (series D). Studies were carried out without or with the pretreatment with placebo or loxiglumide, a specific antagonist of type A CCK receptors. In series A, the gastric secretion obtained by aspiration technique was measured after secretagogues (MSF, caerulein, GRP or p-gastrin), whereas in series B, C, and D intragastric pH was measured before and after test meal and plasma gastrin, CCK and somatostatin were assayed by specific radioimmunoassays. In healthy subjects, MSF increased gastric acid outputs to about 36% of p-gastrin maximum and treatment with loxiglumide failed to affect this secretion. Standard meal enhanced acid output to about 50% of p-gastrin maximum and raised plasma levels of gastrin, CCK but not somatostatin. The pretreatment with loxiglumide resulted in further increase both in gastric acid secretion and plasma gastrin and CCK, while somatostatin level was significantly reduced. Infusion of graded doses of caerulein or GRP resulted in dose-dependent stimulation of gastric acid secretion reaching, respectively, 35% and 25% of p-gastrin maximum. When loxiglumide was added, the acid responses to caerulein and GRP were further increased by 2-3 folds, attaining a peak similar to the p-gastrin maximum. Administration of loxiglumide resulted in a significant increase in plasma gastrin and CCK responses to GRP, whereas plasma somatostatin was not significantly altered. Addition of fat to standard meal prolonged gastric emptying of this meal by about 50% both in healthy subjects and DU patients (series B). Fat in healthy subjects significantly increased and prolonged intragastric pH after the meal while reducing the increments in plasma gastrin and enhancing plasma CCK without alteration of plasma somatostatin. Pretreatment with loxiglumide significantly reduced postprandial pH from control 4.8 to 2.5 and reversed the changes in pH caused by addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin were attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin or CCK. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin. Intragastric application of standard meal of pH 3.0 in healthy subjects and DU patients (series C) resulted in significantly lower median 3 h intragastric pH as compared to that after meal of pH 6.5. After pretreatment with loxiglumide, the median pH after meals of both pHs was significantly lower in healthy subjects but not in DU patients. This reduction in pH was accompanied by more pronounced increase in plasma gastrin response to a meal of pH 6.5 only in healthy controls but not in DU subjects and by a significant increase in plasma CCK and decrease in plasma somatostatin.