Abstract
CB1 receptor agonist anandamide, the synthetic CB1 receptor agonist WIN 55,212-2 and the CBI specific antagonist SR141716 on smooth muscle membrane potentials following electrical neuronal stimulation. Experiments were performed in wild-type as well as in CB1deficient mice. Results: Focal electrical stimulation of the myenteric plexus induced a fast excitatory junction potential (EJP; abolished by atropine) followed by a fast inhibitory junction potential (fliP; reduced by apamin) and a slow inhibitory junction potential (slJP; abolished by L-NNA). None of the used drugs had an influence on the resting membrane potential. Addition of anandamide (10-6-10-5M) in the wildtype abolished the EJP while leaving the flJP and the slJP unchanged. The more potent CB1 agonist WIN 55,212-2 reduced the EJP and the flJP but did not change the sUP. In the CB1 deficient mice anandamide and WIN 55,212-2 had no effect. SR141716 when given alone increased the EJP in wildtype mice while leaving the IJPs in the wildtype and the EJPs and IJPs in the knockout mice unchanged. 5R141716 reversed all anandamide and WIN 55,212-2 effects in the wildtype mice. In the CB 1 defficient mice, the EJFs are significantly increased compared to wildtype, the UPs remein unaltered. Conclusions: We conclude that the CB1 eannabinoidreceptor modulates excitatory and inhibitory neurotranamission in the mouse colon. Since in the CB1 deficient mice EJPs are sigmficantly increased these findings strongly suggesting a physiologic involvement of CB1 receptors in cholinergic neurotransmission. Finally, our study supports that no other receptors than CB1 are involved in the anandamide action on mouse distal colon since the endogenous agonist anandamide had no effect in CB1deficient mice.
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