Cannabinoid 1 receptors modulate intestinal sensory and motor function in rat

Abstract

Cannabinoid receptors are involved in visceral pain perception and control of intestinal motility in vivo. The underlying mechanisms are not well characterized. We aimed to determine whether the cannabinoid-1 (CB(1)) receptor modulates intestinal afferent nerve discharge and the peristaltic reflex. Rats were anesthetized and intestinal segments were removed. Afferent nerve discharge from a mesenteric nerve was investigated in vitro in the presence of the CB(1) antagonist SR 141716A or the CB(1) agonist WIN 55212-2. The myenteric peristaltic reflex was induced by electrical field stimulation and influence of SR 141716A or WIN 55212-2 was recorded. Afferent nerve discharge to the algesic mediator bradykinin was reduced to 11 +/- 5.1 imp s(-1) following pretreatment with SR 141716A and unchanged after WIN 55212-2 compared to 63 +/- 15.4 imp s(-1) in controls. At maximum distension pressure (80 cmH(2)O) during ramp distension, 92 +/- 12.4 imp s(-1) were reached following SR 141716A compared to 260 +/- 13.2 in vehicle controls and 227 +/- 15.4 in WIN 55212-2 pretreated animals. In contrast, afferent discharge to 5-HT (500 micromol L(-1)) was increased to 75 +/- 24.6 imp s(-1) following WIN 55212-2 compared to 18 +/- 5.9 imp s(-1) in controls, whereas SR 141716A had no effect. Ascending neuronal contractions were dose-dependently attenuated in the presence of SR 141716A and latency of these contractions was reduced. WIN 55212-2 had opposite effects that were abolished by SR 141716A. Activation of the CB(1) receptor differentially alters afferent intestinal nerve sensitivity to bradykinin, 5-HT, and noxious mechanical distension, while it strengthens ascending neuronal contractions. Further studies are needed to determine the physiological relevance of these observations.