title: Inhibitory effects of cannabinoid receptor ligands on electrically-evoked responses in rat isolated tracheal ring segments.
abstract: We have examined the possible existence of cannabinoid receptors in the isolated rat tracheal ring segments by studying the effects of some cannabinoid receptor ligands on electrically-induced contractions. Anandamide (10(-8)-3 x 10(-5)m), an endogenous ligand for cannabinoid receptors, and WIN 55,212-2 (10(-9)-3 x 10(-5)m), a moderately selective CB(2)agonist, inhibited electrically evoked contractions of the rat tracheal ring segments in a concentration-related manner. Addition of phentolamine (10(-6)m) to Krebs Henseleit solution to block alpha(2)-adrenoceptors did not affect anandamide-induced inhibition of the electrically evoked contractions. The EC(25)(-log m) values were 5.25+/-0.2 and 5.8+/-0. 4 for anandamide and WIN 55,212-2, respectively. The maximal inhibition produced by the highest concentration of the agonists used was 51.4+/-5.8% for anandamide and 35.1+/-19.5% for WIN 55, 212-2. WIN 55,212-3 also produced a concentration-dependent inhibition of the electrically evoked contractions. The maximal inhibition produced by WIN 55,212-3 was 15.8+/-2.4. The inhibitory effects of anandamide and WIN 55,212-2 were not attenuated by SR141716A (10(-6)m), a selective CB(1)receptor antagonist. Anandamide (10(-8)-3 x 10(-5)m) did not relax rat tracheal ring segments pre-contracted with carbachol (10(-6)m). These results suggest that anandamide and WIN 55,212-2 produce pre-junctional inhibitory effects in the rat trachea and that these effects were likely mediated through cannabinoid CB(2)receptors. These effects were probably non-cannabinoid receptor-mediated considering the high concentrations of the agents required to produce inhibitory responses and the effectiveness of WIN 55,212-3.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Safat, 13110, Kuwait.
authors.forename: M H
authors.initials: MH
authors.lastname: Yousif
authors.forename: M A
authors.initials: MA
authors.lastname: Oriowo
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines; D002186:Cannabinoids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D063388:Endocannabinoids; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D009281:Naphthalenes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D000077285:Rimonabant; D013779:Tetrodotoxin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D048588:Benzoxazines; D002186:Cannabinoids; C469526:Cnr2 protein, rat; D063388:Endocannabinoids; D008024:Ligands; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013779:Tetrodotoxin; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant; C078814:anandamide