title: The contractile effect of anandamide in the guinea-pig small intestine is mediated by prostanoids but not TRPV1 receptors or capsaicin-sensitive nerves.
abstract: Although exogenous and endogenous cannabinoid receptor agonists have well-documented inhibitory effects on gastrointestinal motility, a TRPV1 receptor-mediated excitatory action of anandamide (arachidonoyl ethanolamide, AEA) in the guinea-pig ileum strip has also been described. We used in vitro capsaicin desensitization for assessing the possible participation of sensory neurons in the contractile effect of anandamide on the guinea-pig whole ileum, as well as autonomic drugs and a cyclooxygenase inhibitor for characterizing this response. Isolated organ experiments were used with isotonic recording. Contractions induced by anandamide (1 or 10 μM) were strongly inhibited by tetrodotoxin, indomethacin or atropine plus a tachykinin NK(1) receptor antagonist, but weakly to moderately reduced by atropine alone and partly diminished by the fatty acid amide hydrolase inhibitor URB 597. Neither capsaicin pre-treatment nor the TRPV1 receptor antagonist BCTC, the ganglionic blocking drug hexamethonium or cannabinoid (CB1 or CB2 ) receptor antagonists, influenced the effect of anandamide. It is concluded that the capsaicin-insensitive, neuronal excitatory effect of anandamide in the intestine is most probably mediated by cyclooxygenase products. Such a mechanism may also play a role at other sites in the mammalian body.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University Medical School of Pécs, Pécs, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Dékány
authors.forename: Rita
authors.initials: R
authors.lastname: Benko
authors.forename: Veronika
authors.initials: V
authors.lastname: Szombati
authors.forename: Lorand
authors.initials: L
authors.lastname: Bartho
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D063388:Endocannabinoids / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D018689:Sensory System Agents / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D011453:Prostaglandins; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D002211:Capsaicin; C078814:anandamide; D007213:Indomethacin