-Original-

Effects of Cannabinoids on Colonic Muscle Contractility and Tension in Guinea Pigs

Naoshige Harada¹, Kayo Nemoto¹, Tadao Okamura², Norifumi Ninomiya^1,3, Hidenori Suzuki² and Yasuhiro Yamamoto¹

¹Department of Emergency and Critical Care Medicine, Nippon Medical School
²Department of Pharmacology, Nippon Medical School
³Emergency Medicine The George Washington University School of Medicine and Health Sciences

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.
Design: Prospective experimental observations using the cannabinoid agonists 2-arachidonoylglycerol (2-AG) and WIN55212-2; a cannabinoid antagonist, AM281; and ion-channel antagonist.
Setting: University research laboratory
Subjects: Thirty guinea pigs (20 for in vivo study, 10 for in vitro)
Measurements and main 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 Ca²⁺-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.

J Nippon Med Sch 2005; 72: 43-51

Keywords
cannabinoids, guinea pig, colon, contractility, tension, CB1 recepter

Correspondence to
Naoshige Harada, MD, Department of Emergency and Critical Care Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
naoshige@musashino.jrc.or.jp

Received, September 28, 2004
Accepted, November 9, 2004