Adenosine, by acting on adenosine A1 and A2A receptors, is known to antagonistically modulate dopaminergic neurotransmission. We have recently reported that nonselective adenosine receptor antagonists (caffeine and 3,7-dimethyl-1-propargylxanthine) can partially substitute for the discriminative-stimulus effects of methamphetamine. In the present study, by ...

This review focuses on the potential role of site- and event-selective adenosinergic drugs in the treatment of cardiovascular diseases. Adenosine is released from the myocardium and vessels in response to various forms of stress and acts on four receptor subtypes (A1, A2A, A2B and A3). Adenosine is an important endogenous substance ...

Tardive dyskinesia is a syndrome characterized by repetitive involuntary movements usually involving the mouth, face and tongue. It is considered as the late onset adverse effect of prolonged administration of typical neuroleptic drugs. Adenosine is now widely accepted as the major inhibitory neuromodulators in the central nervous system besides GABA. Both, agonists of ...

Whether adenosine, a crucial regulator of the developing cardiovascular system, can provoke arrhythmias in the embryonic/fetal heart remains controversial. Here, we aimed to establish a mechanistic basis of how an adenosinergic stimulation alters function of the developing heart. Spontaneously beating hearts or dissected atria and ventricle obtained from 4-day-old chick ...

To clarify if the behavioral interaction between ethanol and adenosine reported previously occur centrally or due to a peripheral hemodynamic change, the effect of i.c.v. adenosine agonists, N6-(R-phenylisopropyl)adenosine (R-PIA), N6-(S-phenylisopropyl)adenosine, 5'-(N-cyclopropyl)-carboxamidoadenosine, antagonists, theophylline and 8-p-(sulfophenyl)theophylline as ...

It is well known that the uncoupling between local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF), i.e. decrease in LCBF rates with high LCGU, is frequently associated with seizure-induced neuronal damage. This study was performed to assess if the neuroprotective effect of the adenosinergic A(1) receptor ...

Adenosine has been termed a retaliatory metabolite and its neuroprotective effects have been implicated in the hypoxia tolerance of several species; however, its role in the invertebrate CNS remains unclear. To determine if adenosine modulates neuronal activity in invertebrate neurons, we conducted whole-cell recordings from neurons in the central ring ganglia of the anoxia-tolerant pond snail ...

Nucleoside transport sites in rat brain membrane preparations were labeled with (/sup 3/H)nitrobenzylthioinosine ((/sup 3/H) NBI), a potent inhibitor of nucleoside transport systems. The membranes contained a single class of very high affinity binding sites with K/sub D/ and B/sub max/ values of 0.06 nM and 147 fmol/mg of protein, respectively. The displacement of (/sup 3/H)NBI binding by various ...

The cholinergic system of the basal forebrain (BF) is hypothesized to play an important role in behavioural and electrocortical arousal. Adenosine has been proposed as a sleep-promoting substance that induces sleep by inhibiting cholinergic neurons of the BF and brainstem. However, adenosinergic influences on the activity of BF neurons in naturally awake and sleeping animals ...

TrpA1 is an ion channel involved in nociceptive and inflammatory pain. It is implicated in the detection of chemical irritants through covalent binding to a cysteine-rich intracellular region of the protein. While performing an HTS of the Pfizer chemical collection, a class of pyrimidines emerged as a non-reactive, non-covalently binding family of ...

Adenosinergic systems have been implicated in anxiety-like states, as caffeine can induce a state of anxiety in human beings. Caffeine is an antagonist at A(1) and A(2) adenosine receptors but it remains unclear whether anxiety is mediated by one or both of these. As the adenosinergic system is rather conserved, we opted to pursue these questions using ...

The possible role of brain adenosine (Ado) in acute ethanol-induced alteration in glucose utilization in the cerebellum and brain stem was investigated. The slices were incubated for 100 min in a glucose medium in Warburg flasks using {sup 14}C-glucose as a tracer. Trapped {sup 14}CO{sub 2} was counted to estimate glucose utilization. Ethanol markedly increased the glucose utilization in both ...

Methylphenidate (MPH) is the preferred treatment used for attention-deficit/hyperactivity disorder (ADHD). Recently, misuse for MPH due to its apparent cognitive enhancer properties has been reported. Adenosine is a neuromodulator known to exert influence on the dopaminergic neurotransmission, which is the main pharmacological target of MPH. We have reported that an overdosage of MPH up-regulates ...

The perifornical-lateral hypothalamic area (PF-LHA) plays a central role in the regulation of behavioral arousal. The PF-LHA contains several neuronal types including wake-active hypocretin (HCRT) neurons that have been implicated in the promotion and/or maintenance of behavioral arousal. Adenosine is an endogenous sleep factor and recent evidence suggests that activation and blockade of adenosine ...

It has been shown that adenosine deaminase (ADA; EC 3.5.4.4) behaves as an ecto-enzyme anchored to membrane proteins, among them A(1) adenosine receptors (A(1)Rs). Bovine ADA interacts with A(1)Rs from many species and regulates agonists binding to receptors in an activity-independent form. ...

Prolonged activation of opioid receptors followed by agonist removal leads to adenylyl cyclase (AC) superactivation. In this study, we examined in CHO cells stably expressing the human or rat kappa opioid receptor (hkor or rkor) whether agonists had differential abilities to induce AC superactivation and whether the hkor and rkor exhibited differential AC ...

Previous studies have supported the hypothesis that macromolecular synthesis occurs in the brain during sleep as a response to prior waking activities and that prostaglandin D₂ (PGD₂) is an endogenous sleep substance whose effects are dependent on adenosine A_2a receptor-mediated signaling. We compared gene expression in the ...

Dec 30, 1991 ... The ability of the following drugs to reduce motion sickness in the cats was examined: amphetamines, adenosinergic drugs, opioid antagonists ...

Ethanol affects the function of neurotransmitter systems, resulting in neuroadaptations that alter neural excitability. Adenosine is one such receptor system that is changed by ethanol exposure. The current review is focused on the A(1) and the A(2A) receptor subtypes in the context of ethanol-related neuroadaptations and ethanol withdrawal because these subtypes (i) are activated by basal levels ...

Intense efforts of many pharmaceutical companies and academicians in the A(1) adenosine receptor (AR) field have led to the discovery of clinical candidates that are antagonists, agonists, and allosteric enhancers. The A(1)AR antagonists currently in clinical development are KW3902, BG9928, and SLV320. All three have high affinity for the human (h) ...

A(1) adenosine receptor (AR) agonists are neuroprotective, cardioprotective, and anxiolytic. (N)-Methanocarba adenine nucleosides designed to bind to human A(1)AR were truncated to eliminate 5'-CH(2)OH. This modification previously converted A(3)AR agonists into ...

Highly malignant human gliomas overexpress the G-protein-coupled chemoattractant receptor formyl peptide receptor (FPR1), which promotes tumor progression when activated. Our previous studies demonstrated that necrotic glioblastoma cells release chemotactic agonist(s) that activate FPR1 on viable tumor cells. In the present study, we identified an FPR1 ...

Post traumatic seizures (PTS) are a significant complication from traumatic brain injury (TBI). Adenosine, a major neuroprotective and neuroinhibitory molecule, is important in experimental epilepsy models. Thus, we investigated the adenosine A1 receptor (A1AR) gene and linked it with clinical data extracted for ...

Adenosine plays an important neuroprotective role in brain, usually mediated by the activation of adenosine A(1) receptors. Prolonged activation of a G-protein-coupled receptor generally leads to the partial loss of the responsiveness of receptor-mediated transduction pathways (desensitization). Rat immature cortical neurons were treated with 100nM ...

Extensive experience from randomized clinical trials demonstrates the efficacy of GLP-1 agonists and DPP-4 inhibitors as monotherapy and in combination with metformin and other agents, although reductions in FPG and PPG, and consequently A1C, are greater with GLP-1 agonists than with DPP-4 inhibitors. This ...

Hyperthermic prolongation of the laryngeal chemoreflex (LCR) in decerebrate piglets is prevented or reversed by gamma-aminobutyric acid A (GABA_A) receptor antagonists and adenosine A_2A (Ad-A_2A) receptor antagonists administered in the nucleus of the solitary tract (NTS). Therefore, we tested the hypothesis that enhanced ...

Sleep fragmentation (SF) impairs the restorative/cognitive benefits of sleep via as yet unidentified alterations in neural physiology. Previously, we found that hippocampal synaptic plasticity and spatial learning are impaired in a rat model of SF which utilizes a treadmill to awaken the animals every 2 min, mimicking the frequency of awakenings observed in human sleep apnea patients. Here, we ...

Cytochrome P450 enzymes are involved in a number of steps in ecdysteroid (moulting hormone) homeostasis in insects. We report the cloning and characterization of an ecdysteroid agonist-responsive cytochrome P450, CYP18A1, from the cotton leafworm, Spodoptera littoralis. Northern blot analysis showed that the mRNA transcript was ...

Disclosed are dopamine agonist and opioidergic compositions and methods for their use in the treatment of alcoholism. The invention discloses compounds and therapeutic kits useful in the treatment of alcoholics having the A1 allele of the dopamine receptor D2 gene. Also disclosed are methods of treating alcoholics having the A1/A1 or A1/A2 DRD2 genotype comprising ...

A class of innate receptors called the triggering receptors expressed on myeloid cells (TREM) has been discovered and shown to be involved in innate inflammatory responses. The TREM family has been found in the chicken genome and consists of one activating gene (TREM-A1) and two inhibitory genes (TREM-B1 and TREM-B2). However, to date, there have been no ...

In patients with paroxysmal non-kinesigenic dyskinesias, episodes of dystonia can be provoked by stress and also by methylxanthines (e.g. caffeine), which inhibit adenosine A(1)/A(2A) receptors. In the dt(sz) mutant hamster, a model of this movement disorder, adenosine A(1) receptor antagonists were previously ...

Pharmacological characterization of adenosine A(1) and A(2A) receptors in human brain caudate nucleus membranes led to non-cooperative binding of radiolabelled ligands. In human caudate nucleus but not in cortex, the agonist binding to A(1) receptors was modulated by the agonist binding to A(2A) receptors ...