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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/G539    most recent 00064.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Grider, J. R. Articles by Martin, B. R. PubMed PubMed Citation Articles by Grider, J. R. Articles by Martin, B. R.

NEUROREGULATION AND MOTILITY

Modulation of motor and sensory pathways of the peristaltic reflex by cannabinoids

¹Department of Physiology and Biophysics, ²Department of Internal Medicine, Division of Gastroenterology, ³Department of Pharmacology and Toxicology and the Virginia Program in Enteric Neuromuscular Sciences (VPENS), Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia

Submitted 19 February 2009 ; accepted in final form 26 June 2009

Cannabinoids have long been known to be potent inhibitors of intestinal and colonic propulsion. This effect has generally been attributed to their ability to prejunctionally inhibit release of acetylcholine from excitatory motor neurons that mediate, in part, the ascending contraction phase of the peristaltic reflex. In the present study we examined the effect of cannabinoids on the other transmitters known to participate in the peristaltic reflex using a three-compartment preparation of rat colon that allows separation of ascending contraction, descending relaxation, and the sensory components of the reflex. On addition to the orad motor compartment, anandamide decreased and AM-251, a CB-1 antagonist, increased ascending contraction and the concomitant substance P (SP) release. Similarly, on addition to the caudad motor compartment, anandamide decreased and AM-251 increased descending relaxation and the concomitant vasoactive intestinal peptide (VIP) release. On addition to the central sensory compartment, anandamide decreased and AM-251 increased both ascending contraction and SP release orad, and descending relaxation and VIP release caudad. This suggested a role for CB-1 receptors in modulation of sensory transmission that was confirmed by the demonstration that central addition of anandamide decreased and AM-251 increased release of the sensory transmitter, calcitonin gene-related peptide (CGRP). We conclude that the potent antipropulsive effect of cannabinoids is the result of inhibition of both excitatory cholinergic/tachykininergic and inhibitory VIPergic motor neurons that mediate ascending contraction and descending relaxation, respectively, as well as inhibition of the intrinsic sensory CGRP-containing neurons that initiate the peristaltic reflex underlying propulsive motility.

endocannabinoid; cannabinoid receptors; enteric nervous system; peristalsis; neuropeptides