While most of the studies concerning the role of cannabinoids on gastric motility have focused the attention on the gastric emptying in in vivoanimal models, there is little information about the cannabinoid peripheral influence in the stomach. In addition, the functional features of CB2receptors in the gastrointestinal tract have been poorly characterized.The purpose of the present study was to investigate the effects of cannabinoid drugs on the excitatory cholinergic and inhibitory non-adrenergicnon-cholinergic (NANC) neurotransmission in mouse isolated gastric preparations. Intraluminal pressure from isolated whole stomachwas recordedand mechanical responses induced by electrical field stimulation (EFS) were analyzed in different experimental conditions.EFS (0.5 ms duration, supramaximal voltage, in trains of 5 s, 2–16 Hz) caused a cholinergic contraction, which was abolished by atropine ortetrodotoxin (TTX). The cannabinoid receptor agonist, WIN 55,212-2, the endogenous ligand, anandamide, the selective CB1 receptor agonistACEA, and the selective CB2 receptor agonists, JWH015 and JWH133, produced a concentration-dependent reduction of the EFS-evoked cholinergiccontractions. SR141716A, CB1 receptor antagonist, significantly attenuated the inhibitory effects induced by WIN 55,212-2, anandamideor ACEA, without affecting those caused by JWH133. AM630, CB2 receptor antagonist, reduced the inhibitory effects induced by WIN 55,212-2, anandamide, JWH015 or JWH133, without affecting those caused by ACEA. The joint application of SR141716A and AM630 was able offully preventing the WIN 55,212-2 and anandamide actions. The cannabinoid antagonists failed per se to affect the neurally evoked responses.Cannabinoids did not modify the contractions produced by exogenous carbachol. In the presence of atropine and guanethidine (NANC conditions)EFS-induced TTX-sensitive relaxation consisting in an early and rapid component followed by a second slow phase, which were unaffected bycannabinoid drugs. In conclusion, the present results suggest that cannabinoids play a prejunctional modulatory role on the cholinergic excitatorytransmission without affecting the NANC inhibitory transmission. In addition, this study provides experimental evidence that also the activationof CB2 receptors is able to reduce cholinergic neurotransmission in the mouse stomach.
|Numero di pagine||8|
|Stato di pubblicazione||Published - 2007|
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