Mechanism of gastrointestinal abnormal motor activity induced by cisplatin in conscious dogs.
OBJECTIVE
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.


CONCLUSIONS
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.
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.
Hiroyuki
H
Ando
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.
Erito
E
Mochiki
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.
Tetsuro
T
Ohno
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.
Mitsuhiro
M
Yanai
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.
Yoshitaka
Y
Toyomasu
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.
Kyoichi
K
Ogata
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.
Yuichi
Y
Tabe
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.
Ryuusuke
R
Aihara
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.
Toshihiro
T
Nakabayashi
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.
Takayuki
T
Asao
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.
Hiroyuki
H
Kuwano
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003243:Consciousness; D004285:Dogs; D005753:Gastric Mucosa / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D007419:Intestinal Secretions / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D059326:Serotonergic Neurons / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000008:administration & dosage / Q000097:blood; D013270:Stomach / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology; D014839:Vomiting / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology
D000970:Antineoplastic Agents; D012701:Serotonin; D002945:Cisplatin
5-hydroxytryptamine; Abnormal motor activity; Cisplatin; Dog; Emesis