title: Modulation of motor and sensory pathways of the peristaltic reflex by cannabinoids.
abstract: 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.
authors: Dept. of Physiology and Biophysics, Box 980551, MCV campus, Virginia Commonwealth Univ., Richmond, VA 23298-0551, USA. jgrider@vcu.edu
authors: John R
authors: JR
authors: Grider
authors: Sunila
authors: S
authors: Mahavadi
authors: Yan
authors: Y
authors: Li
authors: Li-Ya
authors: LY
authors: Qiao
authors: John F
authors: JF
authors: Kuemmerle
authors: Karnam S
authors: KS
authors: Murthy
authors: Billy R
authors: BR
authors: Martin
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D003106:Colon / Q000294:innervation*; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition; D010528:Peristalsis / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; C469526:Cnr2 protein, rat; D063388:Endocannabinoids; D007211:Indoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; C103505:AM 251; D015740:Calcitonin Gene-Related Peptide; C094023:iodopravadoline; C078814:anandamide