Cannabinoid agonists inhibit the activation of 5-HT3 receptors in rat nodose ganglion neurons.
1. Effects of cannabinoid agonists on the serotonin (5-HT)3 receptor-mediated current were investigated in rat nodose ganglion neurons. Anandamide, Win 55212-2, and CP55940 inhibited the 5-HT-induced current in a concentration dependent manner. IC50 values were 190, 310, and 94 nM for anandamide, Win 55212-2, and CP55940, respectively, and 1.6 microM for the nonpsychoactive enantiomer CP56667. This inhibition was slowly developing, noncompetitive, not dependent on membrane potential, and not affected by adenosine 3',5'-cyclic monophosphate (cAMP) analogues, guanosine-5'-O-(2-thiodiphosphate) (GDP-beta-S), and opioid receptor antagonist naltrexone. These data suggest that 5-HT3 receptor ion-channel is a site acted upon by cannabinoid agonists in the nervous system, and the action of cannabinoid agonists on 5-HT3 receptors may be a possible mechanism for some of the behavioral effects of cannabinoids, such as antiemesis and analgesia.
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Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines; D002186:Cannabinoids / Q000819:agonists*; D003511:Cyclohexanols / Q000494:pharmacology; D063388:Endocannabinoids; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D053284:Polyunsaturated Alkamides; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*
D001095:Arachidonic Acids; D048588:Benzoxazines; D002186:Cannabinoids; D003511:Cyclohexanols; D063388:Endocannabinoids; D009025:Morpholines; D009281:Naphthalenes; D053284:Polyunsaturated Alkamides; D011985:Receptors, Serotonin; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; C078814:anandamide