• Myenteric plexus;
  • cannabinoids;
  • intestinal motility;
  • anandamide;
  • small intestine
  • 1
    The 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).
  • 2
    The 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.
  • 3
    Apamin (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.
  • 4
    The 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).
  • 5
    In 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.
  • 6
    It 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