Brief Article
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World J Gastroenterol. Oct 21, 2013; 19(39): 6604-6612
Published online Oct 21, 2013. doi: 10.3748/wjg.v19.i39.6604
Effects of 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists on gastrointestinal motor activity in dogs
Hiroki Morita, Erito Mochiki, Nobuyuki Takahashi, Kiyoshi Kawamura, Akira Watanabe, Toshinaga Sutou, Atsushi Ogawa, Mitsuhiro Yanai, Kyoichi Ogata, Takaaki Fujii, Tetsuro Ohno, Souichi Tsutsumi, Takayuki Asao, Hiroyuki Kuwano
Hiroki Morita, Erito Mochiki, Akira Watanabe, Toshinaga Sutou, Atsushi Ogawa, Mitsuhiro Yanai, Kyoichi Ogata, Takaaki Fujii, Tetsuro Ohno, Souichi Tsutsumi, Takayuki Asao, Hiroyuki Kuwano, Department of General Surgical Science (Surgery 1), Gunma University, Graduate School of Medicine, Gunma 371-8511, Japan
Nobuyuki Takahashi, Kiyoshi Kawamura, RaQualia Pharma Inc., Research and Development, 5-2 Taketoyo, Aichi 470-2341, Japan
Author contributions: Morita H drafted the manuscript under the direction of Mochiki E; Takahashi N, Kawamura K, Watanabe A, Sutou T, Ogawa A, Yanai M, Ogata K, Fujii T, Tsutsumi S and Asao T were involved in the analysis and interpretation of data; Kuwano H made the final corrections and comments.
Correspondence to: Hiroki Morita, MD, PhD, Department of General Surgical Science (Surgery 1), Gunma University, Graduate School of Medicine, 3-39-22 Showamachi, Maebashi, Gunma 371-8511, Japan. m09702031@gunma-u.ac.jp
Telephone: +81-27- 2208224 Fax: +81-27-2208230
Received: April 10, 2013
Revised: August 22, 2013
Accepted: September 15, 2013
Published online: October 21, 2013
Abstract

AIM: To study the effects of 5-hydroxytryptamine (5-HT) receptor antagonists on normal colonic motor activity in conscious dogs.

METHODS: Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B, 5-HT3 and 5-HT4 receptor antagonist administration. The force transducers were implanted on the serosal surfaces of the gastric antrum, terminal ileum, ileocecal sphincter and colon. Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state. The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.

RESULTS: 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum. The 5-HT3 and 5-HT4 receptor antagonists inhibited phase III of the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity. In the proximal colon, the inhibitory effect was dose dependent. Dose dependency, however, was not observed in the distal colon. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.

CONCLUSION: The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.

Keywords: 5-hydroxytryptamine receptor antagonist, Colonic motility, Irritable bowel syndrome

Core tip: Previous studies have investigated the effects of 5-hydroxytryptamine (5-HT) receptor antagonists on abnormal colonic motor activity, following either the administration of 5-HT or stress induction. This study is the first to investigate the effects of 5-HT receptor antagonists on normal colonic motor activity in dogs. 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity. A 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity. 5-HT3 and 5-HT4 receptor antagonists may also be used as premedications for colonoscopy. A 5-HT2B receptor antagonist may be used for the treatment of diarrhea-predominant irritable bowel syndrome without the side effect of constipation.