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Am J Physiol Gastrointest Liver Physiol 292: G1037-G1044, 2007. First published December 7, 2006; doi:10.1152/ajpgi.00419.2006 Free Article
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NEUROREGULATION AND MOTILITY

Restraint stress stimulates colonic motility via central corticotropin-releasing factor and peripheral 5-HT3 receptors in conscious rats

Yukiomi Nakade,1 Hiroyuki Fukuda,1 Masahiro Iwa,1 Kiyoshi Tsukamoto,1,2 Hidenori Yanagi,2 Takehira Yamamura,2 Christopher Mantyh,1 Theodore. N. Pappas,1 and Toku Takahashi1

1Department of Surgery, Duke University Medical Center and Durham Veterans Affairs Medical Center, Durham, North Carolina; and 2Department of Second Surgery, Hyogo College of Medicine, Nishinomiya, Japan

Submitted 10 September 2006 ; accepted in final form 29 November 2006

Although restraint stress accelerates colonic transit via a central corticotropin-releasing factor (CRF), the precise mechanism still remains unclear. We tested the hypothesis that restraint stress and central CRF stimulate colonic motility and transit via a vagal pathway and 5-HT3 receptors of the proximal colon in rats. 51Cr was injected via the catheter positioned in the proximal colon to measure colonic transit. The rats were subjected to a restraint stress for 90 min or received intracisternal injection of CRF. Ninety minutes after the administration of 51Cr, the entire colon was removed, and the geometric center (GC) was calculated. Four force transducers were sutured on the proximal, mid, and distal colon to record colonic motility. Restraint stress accelerated colonic transit (GC of 6.7 ± 0.4, n = 6) compared with nonrestraint controls (GC of 5.1 ± 0.2, n = 6). Intracisternal injection of CRF (1.0 µg) also accelerated colonic transit (GC of 7.0 ± 0.2, n = 6) compared with saline-injected group (GC of 4.6 ± 0.5, n = 6). Restraint stress-induced acceleration of colonic transit was reduced by perivagal capsaicin treatment. Intracisternal injection of CRF antagonists (10 µg astressin) abolished restraint stress-induced acceleration of colonic transit. Stimulated colonic transit and motility induced by restraint stress and CRF were significantly reduced by the intraluminal administration of 5-HT3 antagonist ondansetron (5 x 10–6 M; 1 ml) into the proximal colon. Restraint stress and intracisternal injection of CRF significantly increased the luminal content of 5-HT of the proximal colon. It is suggested that restraint stress stimulates colonic motility via central CRF and peripheral 5-HT3 receptors in conscious rats.

ondansetron; vagal afferent; pelvic nerves; enteric nervous system



Address for reprint requests and other correspondence: T. Takahashi, Surgical Service 112, VA Medical Center,, 508 Fulton St., Durham, NC 27705 (e-mail: ttakahas{at}duke.edu)




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