Aim: 

Although it is well accepted that cannabinoids, acting on CB1 receptors, modulate intestinal motility through reduction of cholinergic neurotransmission, it is not known whether the endocannabinoids are involved in more complex circuits underlying intestinal propulsion and if they interact with other systems. Because purines play an important role in the modulation of gastrointestinal motor functions, the aim of the present study was to examine the possible interplay between cannabinoid CB1 receptors and purines in the control of spontaneous contractility of longitudinal muscle in mouse ileum.

Methods: 

Longitudinally oriented ileal segments were suspended in an organ bath. The mechanical activity was digitized on an A/D converter, and analysed on a personal computer using the PowerLab/400 system.

Results: 

The selective CB1 receptor agonist, ACEA produced a concentration-dependent reduction of the spontaneous contractions, which was antagonized by SR141716A, CB1 receptor antagonist, and it was almost abolished by tetrodotoxin (TTX), or atropine. The ACEA inhibitory effects were not affected by theophylline, P1 receptor antagonist or by P2Y receptor desensitisation with ADPbS, but they were significantly reduced by PPADS, P2 antagonist, by desensitization of P2 receptors with ATP, by P2X receptor desensitisation with a,b-MeATP or by NF279, P2X receptor antagonist. The contractile response induced by a,b-MeATP, P2X receptor agonist, was virtually abolished by TTX or atropine, suggesting that it was mediated by acetylcholine neural release and significantly reduced by ACEA.

Conclusions: 

The present results suggest that the activation of CB1 receptors reduce acetylcholine neural release in mouse ileum, through a pathway which involves purines acting on P2X receptors.