Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main psychoactive component of marijuana, Delta9-tetrahydrocannabinol (THC), acts in the CNS via type 1 cannabinoid receptors (CB1Rs). The behavioral consequences of THC or synthetic CB1R agonists include suppression of motor activity. One explanation for movement suppression might be inhibition of striatal dopamine (DA) release by CB1Rs, which are densely localized in motor striatum; however, data from previous studies are inconclusive. Here we examined the effect of CB1R activation on locally evoked DA release monitored with carbon-fiber microelectrodes and fast-scan cyclic voltammetry in striatal slices. Consistent with previous reports, DA release evoked by a single stimulus pulse was unaffected by WIN55,212-2, a cannabinoid receptor agonist. However, when DA release was evoked by a train of stimuli, WIN55,212-2 caused a significant decrease in evoked extracellular DA concentration ([DA]o), implicating the involvement of local striatal circuitry, with similar suppression seen in guinea pig, rat, and mouse striatum. Pulse-train evoked [DA]o was not altered by either AM251, an inverse CB1R agonist, or VCHSR1, a neutral antagonist, indicating the absence of DA release regulation by endogenous cannabinoids with the stimulation protocol used. However, both CB1R antagonists prevented and reversed suppression of evoked [DA]o by WIN55,212-2. The effect of WIN55,212-2 was also prevented by picrotoxin, a GABAA receptor antagonist, and by catalase, a metabolizing enzyme for hydrogen peroxide (H2O2). Furthermore, blockade of ATP-sensitive K+ (KATP) channels by tolbutamide or glybenclamide prevented the effect of WIN55,212-2 on DA release. Together, these data indicate that suppression of DA release by CB1R activation within striatum occurs via a novel nonsynaptic mechanism that involves GABA release inhibition, increased generation of the diffusible messenger H2O2, and activation of KATP channels to inhibit DA release. In addition, the findings suggest a possible physiological substrate for the motor effects of cannabinoid agonist administration.
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PMID:Inhibition of striatal dopamine release by CB1 receptor activation requires nonsynaptic communication involving GABA, H2O2, and KATP channels. 1776 79

The prevalence of obesity has been increasing dramatically in the last decades; the major metabolic complication of obesity is insulin resistance and type-2 diabetes because there are pathogenetic mechanisms linking obesity and type-2 diabetes. Diabetes is also rapidly increasing worldwide; such a description of the key stages in the evolution of type-2 diabetes may be of great interest for implementing antidiabetes treatment. In recent times, type-2 diabetes therapy has been based on drugs, which improve insulin sensibility or stimulate insulin secretion or slow down glucose absorption. Recently, an ADA and EASD consensus has been released to develop a common approach for the management of hyperglycaemia in adults. The development of new classes of blood-glucose-lowering medications to supplement the older therapies, such as lifestyle-directed interventions, insulin, sulfonylureas, and metformin, has increased the different possible options for the treatment of type-2 diabetes. Therapeutic approaches aiming to potentiate the biological effects of incretins include degradation-resistant GLP-1 receptor agonists (incretin mimetics), and inhibitors of dipeptidyl peptidase-IV (DPP-IV) activity (incretin enhancers) will be very useful to slow down type-2 diabetes progression. Weight-loss interventions, such as a hypocaloric diet and physical exercise, in addition to agents such as orlistat, sibutramine and cannabinoid receptor antagonists, may have favourable effects upon fat storage, nutrient metabolism and ultimately glucose tolerance or type-2 diabetes. When the therapeutic target is not achieved, insulin with metformin could be suggested, but is this approach the ideal one for all patients? Perhaps it is possible to delay the initiation of insulin therapy, therefore, the actual and future therapeutical options are considered in the present review.
Acta Diabetol 2008 Jun
PMID:Time to insulin in type-2 diabetes: high hurdles or Santiago way? 1840 82