Modulation of the release of endogenous gamma-aminobutyric acid by cannabinoids in the guinea pig ileum.
Interactions between cannabinoid CB(1) and GABA receptors and ligands were investigated in the myenteric plexus-longitudinal muscle of the guinea pig ileum. Electrically evoked contractions of the myenteric plexus-longitudinal muscle were inhibited by the cannabinoid receptor agonist CP55,940 ((-)-cis-3-[2-Hydroxy-4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol), the GABA(B) receptor agonist, baclofen (4-amino-3-(chlorophenyl) butanoic acid), or exogenous GABA. Electrically evoked contractions of the myenteric plexus-longitudinal muscle were also inhibited by the addition of the GABA releasing agent ethylenediamine. CP55,940 (1 nM) or the endogenous cannabinoid anandamide (arachidonyl ethanolamide, 1 microM) reduced the inhibition produced by ethylenediamine, while in contrast, anandamide (10 microM) significantly increased the inhibition produced by ethylenediamine. The results suggest that while there is no interaction between cannabinoid CB(1) and GABA(B) receptors in the myenteric plexus-longitudinal muscle of the guinea pig, cannabinoid CB(1) receptor stimulation reduces the ethylenediamine-evoked GABA release. In addition, anandamide at higher concentrations also potentiates the inhibitory effect of ethylenediamine at least partly by stimulating vanilloid receptors.
Begg
Malcolm
M
Department of Biosciences, University of Hertfordshire, C.P. Snow Building, College Lane, Hatfield, Herts AL10 9AB, UK.
Molleman
Areles
A
Parsons
Mike
M
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology; D004558:Electric Stimulation; D063388:Endocannabinoids; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001095:Arachidonic Acids; D002186:Cannabinoids; D003511:Cyclohexanols; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; C078814:anandamide