Cannabinoid 1 receptors modulate intestinal sensory and motor function in rat.Neurogastroenterol Motil. 2010 Jun; 22(6):672-e205.NM
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.
CONCLUSIONS & INFERENCES
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.