Original Article
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World J Gastroenterol. Nov 14, 2014; 20(42): 15691-15702
Published online Nov 14, 2014. doi: 10.3748/wjg.v20.i42.15691
Mechanism of gastrointestinal abnormal motor activity induced by cisplatin in conscious dogs
Hiroyuki Ando, Erito Mochiki, Tetsuro Ohno, Mitsuhiro Yanai, Yoshitaka Toyomasu, Kyoichi Ogata, Yuichi Tabe, Ryuusuke Aihara, Toshihiro Nakabayashi, Takayuki Asao, Hiroyuki Kuwano
Hiroyuki Ando, Erito Mochiki, Tetsuro Ohno, Mitsuhiro Yanai, Yoshitaka Toyomasu, Kyoichi Ogata, Yuichi Tabe, Ryuusuke Aihara, Toshihiro Nakabayashi, Takayuki Asao, Hiroyuki Kuwano, Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan
Author contributions: Ando H and Mochiki E contributed equally to this work; Ando H, Mochiki E, Ohno T, Yanai M, Toyomasu Y, Ogata K, Tabe Y, Aihara R, Nakabayashi T, Asao T and Kuwano H designed the research; Ando H, Ohno T, Yanai M, Toyomasu Y, Ogata K and Tabe Y performed the research; Ando H, Ohno T, Nakabayashi T and Asao T contributed new reagents/analytic tools; Ando H, Mochiki E, Ohno T, Aihara R, Asao T and Kuwano H analyzed the data; Ando H, Mochiki E and Kuwano H wrote the paper.
Correspondence to: Hiroyuki Ando, MD, PhD, Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. andu07120404andu@yahoo.co.jp
Telephone: +81-27-2208224 Fax: +81-27-2208230
Received: February 22, 2014
Revised: March 25, 2014
Accepted: June 2, 2014
Published online: November 14, 2014
Processing time: 267 Days and 19.3 Hours
Abstract

AIM: To investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration.

METHODS: After the dogs had been given a 2-wk recovery period, all of them were administered cisplatin, and the motor activity was recorded using strain gauge force transducers. Blood and intestinal fluid samples were collected to measure 5-HT for 24 h. To determine whether 5-HT in plasma or that in intestinal fluids is more closely related to abnormal motor activity we injected 5-HT into the bloodstream and the intestinal tract of the dogs.

RESULTS: Cisplatin given intravenously produced abnormal motor activity that lasted up to 5 h. From 3 to 4 h after cisplatin administration, normal intact dogs exhibited retropropagation of motor activity accompanied by emesis. The concentration of 5-HT in plasma reached the peak at 4 h, and that in intestinal fluids reached the peak at 3 h. In normal intact dogs with resection of the vagus nerve that were administered kytril, cisplatin given intravenously did not produce abnormal motor activity. Intestinal serotonin administration did not produce abnormal motor activity, but intravenous serotonin administration did.

CONCLUSION: After the intravenous administration of cisplatin, abnormal motor activity was produced in the involved vagus nerve and in the involved serotonergic neurons via another pathway. This study was the first to determine the relationship between 5-HT and emesis-induced motor activity.

Keywords: Cisplatin; Emesis; 5-hydroxytryptamine; Abnormal motor activity; Dog

Core tip: Previous studies have investigated the motility change unique to cisplatin-induced emesis. This study is the first to investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration. Cisplatin given intravenously produced abnormal motor activity that lasted up to 5 h. In normal dogs with resection of the vagus nerve that were administered 5-HT 3 receptor antagonist (kytril), cisplatin given intravenously did not produce abnormal motor activity. Abnormal motor activity was produced in the involved vagus nerve and in the involved serotonergic neurons via another pathway.