The purpose of the present study was to examine whether cannabinoid receptor agonists influence spontaneous contractile activity oflongitudinal muscle in mouse ileum in vitro. Isolated segments of mouse ileum displayed spontaneous contractions with an amplitude andfrequency of about 300 mg and 30 cpm, respectively. The endocannabinoid anandamide (1–100 μM), the selective cannabinoid CB1 receptoragonist, ACEA (0.1 μM–10 μM), but not the selective cannabinoid CB2 receptor agonist, JWH 133 (0.1 μM–10 μM), reduced in a concentrationdependentmanner the spontaneous mechanical activity. The inhibitory effect consisted in a decrease of the mean amplitude of longitudinalspontaneous contractions, without changes in the resting tone. The inhibitory effect induced by cannabinoids was significantly antagonized by theselective 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-inducedreduction of spontaneous contractions was almost abolished by tetrodotoxin, atropine or apamin and it was unaffected by hexamethonium orNω-nitro-L-arginine methyl ester (L-NAME), inhibitor of nitric oxide synthase. The myogenic contractions evoked by carbachol were notaffected by ACEA. In conclusion, the present results suggest that activation of neural cannabinoid CB1 receptors may play a role in the controlof spontaneous mechanical activity through inhibition of acetylcholine release from cholinergic nerve. Activation of small conductance Ca2+-dependent K+ channels is involved in this action.
|Numero di pagine||7|
|Rivista||European Journal of Pharmacology|
|Stato di pubblicazione||Published - 2008|
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