Excitatory transmission to the circular muscle of the guinea-pig ileum: evidence for the involvement of cannabinoid CB1 receptors
Version of Record online: 11 FEB 2009
1998 British Pharmacological Society
British Journal of Pharmacology
Volume 124, Issue 7, pages 1363–1368, August 1998
How to Cite
Izzo, A. A., Mascolo, N., Borrelli, F. and Capasso, F. (1998), Excitatory transmission to the circular muscle of the guinea-pig ileum: evidence for the involvement of cannabinoid CB1 receptors. British Journal of Pharmacology, 124: 1363–1368. doi: 10.1038/sj.bjp.0701964
- Issue online: 11 FEB 2009
- Version of Record online: 11 FEB 2009
- (Received April 8, 1998, Accepted April 27, 1998)
- Myenteric plexus;
- intestinal motility;
- small intestine
- 1The effect of cannabinoid drugs has been investigated on cholinergic and non-adrenergic non-cholinergic (NANC) contractile responses to the circular smooth muscle of guinea-pig ileum elicited by electrical field stimulation (EFS).
- 2The cannabinoid receptor agonist WIN 55,212-2 (1–1000 nm) and the putative endogenous ligand anandamide (0.1–100 μm) both produced a concentration-dependent inhibition of the cholinergic (9–57% and 1–51% inhibition) and NANC (9–55% and 2–57% inhibition) contractile responses. WIN 55,212-2 and anandamide did not modify the contractions produced by exogenous acetylcholine or substance P.
- 3Apamin (30 nm), a blocker of Ca2+-activated K+ channels, reduced the inhibitory effect of WIN 55,212-2 on cholinergic, but not NANC, contractile response. NG-nitro-l-arginine methyl ester (100 μm), an inhibitor of nitric oxide synthase, or naloxone (1 μm), an opioid receptors antagonist, did not modify the inhibitory effect of WIN 55,212-2 on both cholinergic and NANC contractions.
- 4The inhibitory effects of WIN 55,212-2 and anandamide on both cholinergic and NANC contractile response was competitively antagonized by the cannabinoid CB1 receptor antagonist SR 141716A (10–1000 nm).
- 5In absence of other drugs, SR 141716A (1–1000 nm) enhanced cholinergic (1–45% increase) and NANC (2–38% increase) contractile responses elicited by electrical stimulation, but did not modify the contractions produced by acetylcholine or substance P.
- 6It is concluded that activation of prejunctional cannabinoid CB1 receptors produces inhibition of cholinergic and NANC excitatory responses in the guinea-pig circular muscle. The inhibition of cholinergic (but not NANC) transmission involves activation of apamin-sensitive K+ channels. In addition, an endogenous cannabinoid ligand could inhibit cholinergic and NANC transmission in the guinea-pig ileal circular muscle.
British Journal of Pharmacology (1998) 124, 1363–1368; doi:10.1038/sj.bjp.0701964