Abstract
Cannabinoid receptor agonists inhibit electrically evoked isometric contractions of the myenteric plexus - longitudinal muscle preparation of the guinea-pig small intestine (MPLM), probably by reducing release of acetylcholine (ACh) through the activation of prejunctional CB1 receptors. As CB1 receptors are thought to be negatively coupled through G(i/o) proteins to both N-type Ca2+ channels and adenylate cyclase, we have now further investigated the involvement of CB1 receptors by monitoring the effects of forskolin, 8-bromo-cAMP, 3-isobutyl-1-methylxanthine (IBMX), and extracellular Ca2+ on the ability of the cannabinoid agonist, (+)-WIN 55212 To inhibit electrically evoked contractions of the MPLM (0.1 Hz, 0.5.ms, and 110% maximal voltage). Some experiments were performed with normorphine instead of (+)-WIN 55212. At 10(-7) M, forskolin, 8-bromo-cAMP, and IBMX were found to reduce significantly the maximum inhibitory response to (+)-WIN 55212 by 49.4, 48.4, and 40.2%, respectively, without affecting control contractions or responses to exogenous ACh. Low external Ca2+ (0.64 mM) significantly increased the maximum response to (+)-WIN 55212 and shifted the curve slightly leftwards, whereas high external Ca2+ (5.08 mM) reduced the maximum response by 27.2%. The concentration-response curve to normorphine, which also reduces evoked contractions of this preparation as a result of a presynaptic inhibition of ACh release via opioid mu receptors, was affected similarly. These results support the hypothesis that cannabinoid-induced inhibition in the MPLM is mediated by CB1 receptors.
Original language | English |
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Pages (from-to) | 340-346 |
Number of pages | 7 |
Journal | Canadian Journal of Physiology and Pharmacology |
Volume | 76 |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar 1998 |
Keywords
- cannabinoid
- myenteric
- calcium
- cAMP
- normorphine
- MOUSE VAS-DEFERENS
- PERTUSSIS-TOXIN
- RECEPTOR
- RELEASE
- TRANSMISSION
- ANTAGONIST
- AGONIST
- PROTEIN
- BINDS
- CB1