Cannabinoid CB1 receptor activation modulates spontaneous contractile activity in mouse ileal longitudinal muscle.

The purpose of the present study was to examine whether cannabinoid receptor agonists influence spontaneous contractile activity of longitudinal muscle in mouse ileum in vitro. Isolated segments of mouse ileum displayed spontaneous contractions with an amplitude and frequency of about 300 mg and 30 cpm, respectively. The endocannabinoid anandamide (1–100 μM), the selective cannabinoid CB1 receptor agonist, ACEA (0.1 μM–10 μM), but not the selective cannabinoid CB2 receptor agonist, JWH 133 (0.1 μM–10 μM), reduced in a concentrationdependent manner the spontaneous mechanical activity. The inhibitory effect consisted in a decrease of the mean amplitude of longitudinal spontaneous contractions, without changes in the resting tone. The inhibitory effect induced by cannabinoids was significantly antagonized by the selective cannabinoid CB1 receptor antagonist, SR141716A (0.1 μM), but not by the selective cannabinoid CB2 receptor antagonist, AM630 (0.1 μM). None of the cannabinoid antagonists, at the concentration used, did affect the spontaneous mechanical activity. The ACEA-induced reduction of spontaneous contractions was almost abolished by tetrodotoxin, atropine or apamin and it was unaffected by hexamethonium or Nω-nitro-L-arginine methyl ester (L-NAME), inhibitor of nitric oxide synthase. The myogenic contractions evoked by carbachol were not affected by ACEA. In conclusion, the present results suggest that activation of neural cannabinoid CB1 receptors may play a role in the control of spontaneous mechanical activity through inhibition of acetylcholine release from cholinergic nerve. Activation of small conductance Ca2+- dependent K+ channels is involved in this action.