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

We have studied the effect of SR141716A (0.1-5 mg/kg, i.p.), a cannabinoid CB, receptor antagonist, and WIN (0.1-5 mg/kg, i.p.), a cannabinoid receptor agonist, on acute defaecation and gastrointestinal transit in mice and on intraluminal fluid accumulation in the rat small intestine. SR141716A increased while WIN 55,212-2 decreased defaecation, gastrointestinal transit and fluid accumulation. A per se non-effective dose of SR141716A (0.3 mg/kg) counteracted the inhibitory effect of WIN 55,212-2 (1 mg/kg) on gastrointestinal functions studied. The effect of SR 141716 on both intestinal fluid accumulation in rats and gastrointestinal transit in mice was inhibited by atropine (1 mg/kg, i.p.), but not by hexamethonium (1 mg/kg, s.c.), SR140333 (20 microg/kg, i.p.) or SR48968 (20 microg/kg, i.p.), antagonists of NK1 and NK2 receptors, respectively. These results suggest that intestinal fluid accumulation and motility are inhibited by endogenous cannabinoid(s) acting at the cannabinoid CB1 receptors. This effect may be mediated by mechanisms involving muscarinic cholinoceptors.
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PMID:Defaecation, intestinal fluid accumulation and motility in rodents: implications of cannabinoid CB1 receptors. 993 53

It is well accepted that endogenous cannabinoids and CB1 receptors are involved in the regulation of smooth muscle contractility and intestinal motility, through a mechanism mainly related to reduction of acetylcholine release from cholinergic nerve endings. Because, few data exist on a possible modulatory action of the cannabinoid agents on the non-adrenergic non-cholinergic (NANC) excitatory and inhibitory neurotransmission, the aim of the present study was to investigate the effects of cannabinoid drugs on the NANC responses elicited by electrical field stimulation (EFS) in the circular muscle of mouse proximal colon. Colonic contractions were monitored as changes in endoluminal pressure. In NANC conditions, EFS evoked TTX-sensitive responses, characterized by a relaxation, nitrergic in origin, followed by a contraction. The EFS-evoked contraction was significantly reduced by SR48968, NK2 receptor antagonist, and abolished by co-administration of SR48968 and SR140333, NK1 receptor antagonist, suggesting that it was due to release of tachykinins. The cannabinoid receptor synthetic agonist, WIN55,212-2, the putative endogenous ligand, anandamide, the selective CB1 receptor agonist ACEA, but not the selective CB2 receptor agonist JWH-015, produced a concentration-dependent reduction of the NANC contractile responses, without affecting the NANC relaxation. ACEA or anandamide did not modify the contractions induced by exogenous [beta-Ala(8)]-NKA(4-10), agonist of NK2 receptors. The selective antagonist of CB1 receptors, SR141716A, per se failed to affect the EFS-evoked responses, but antagonized the inhibitory effects of WIN55,212-2, anandamide and ACEA on NANC contractile responses. AM630, CB2 receptor antagonist, did not modify the inhibitory effects of WIN55,212-2 or anandamide. URB597, inhibitor of the fatty acid amide hydrolase, enzyme which catalyze the hydrolysis of anandamide, was without any effect on the NANC evoked responses. We conclude that the activation of prejunctional CB1 receptors produces inhibition of NANC contractile responses in mouse colonic preparations. However, endogenous ligands do not seem to modulate tonically the NANC transmission in mouse colon.
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PMID:Evidence for a modulatory role of cannabinoids on the excitatory NANC neurotransmission in mouse colon. 1757 59

Bladder pain syndrome (BPS) is a clinical syndrome of pelvic pain and urinary urgency-frequency in the absence of a specific cause. Investigating the expression levels of genes involved in the regulation of epithelial permeability, bladder contractility, and inflammation, we show that neurokinin (NK)1 and NK2 tachykinin receptors were significantly down-regulated in BPS patients. Tight junction proteins zona occludens-1, junctional adherins molecule -1, and occludin were similarly down-regulated, implicating increased urothelial permeability, whereas bradykinin B(1) receptor, cannabinoid receptor CB1 and muscarinic receptors M3-M5 were up-regulated. Using cell-based models, we show that prolonged exposure of NK1R to substance P caused a decrease of NK1R mRNA levels and a concomitant increase of regulatory micro(mi)RNAs miR-449b and miR-500. In the biopsies of BPS patients, the same miRNAs were significantly increased, suggesting that BPS promotes an attenuation of NK1R synthesis via activation of specific miRNAs. We confirm this hypothesis by identifying 31 differentially expressed miRNAs in BPS patients and demonstrate a direct correlation between miR-449b, miR-500, miR-328, and miR-320 and a down-regulation of NK1R mRNA and/or protein levels. Our findings further the knowledge of the molecular mechanisms of BPS, and have relevance for other clinical conditions involving the NK1 receptor.
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PMID:MicroRNAs may mediate the down-regulation of neurokinin-1 receptor in chronic bladder pain syndrome. 2000 42