Effects of cannabinoids on colonic muscle contractility and tension in guinea pigs.
OBJECTIVE
While endogenous cannabinoids regulate various physiologic functions, their role in the intestinal tract is unclear. We continuously recorded colonic motility in conscious guinea pigs. Mechanisms of action then were investigated using guinea pig taenia caecum in vitro.


METHODS
Prospective experimental observations using the cannabinoid agonists 2-arachidonoylglycerol (2-AG) and WIN55212-2; a cannabinoid antagonist, AM281; and ion-channel antagonist.


METHODS
University research laboratory.


METHODS
Thirty guinea pigs (20 for in vivo study, 10 for in vitro).


RESULTS
Colonic motility was monitored in vivo using telemetry via a force transducer attached to the guinea pig taenia caecum. Taenias isolated from other guinea pigs were studied in vitro to assess cannabinoid effects on muscle contractions evoked pharmacologically or electrically. Immediately after cannabinoid injection in conscious guinea pigs, taenial relaxation began peaking at 30 to 40 min. In animals pretreated with AM281, a CB1 cannabinoid receptor antagonist, cannabinoid evoked relaxation was less evident. In vitro, cannabinoids suppressed KCl-induced taenial contractions; this suppression was opposed by charybdotoxin, a Ca(2+)-activated K(+)-channel inhibitor, but not AM281. Cannabinoids decreased amplitude of repeated contractions evoked by electrical stimulation (an effect inhibited by AM281) but not muscle tension.


CONCLUSIONS
Cannabinoids decreased intestinal tract tension in vivo, apparently via central CB1 receptors. This differs from peristaltic suppression.
Harada
Naoshige
N
Department of Emergency and Critical Care Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8303, Japan. naoshige@musashino.jr.or.jp
Nemoto
Kayo
K
Okamura
Tadao
T
Ninomiya
Norifumi
N
Suzuki
Hidenori
H
Yamamoto
Yasuhiro
Y
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D048588:Benzoxazines; D001831:Body Temperature / Q000187:drug effects; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D002186:Cannabinoids / Q000819:agonists*; D003106:Colon / Q000187:drug effects*; D004558:Electric Stimulation; D063388:Endocannabinoids; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005989:Glycerides / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009281:Naphthalenes / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology
D001095:Arachidonic Acids; D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D005989:Glycerides; D009025:Morpholines; D009281:Naphthalenes; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C094503:glyceryl 2-arachidonate; C109925:AM 281