Restraint stress stimulates colonic motility via central corticotropin-releasing factor and peripheral 5-HT3 receptors in conscious rats.
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-HT(3) receptors of the proximal colon in rats. (51)Cr 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 (51)Cr, 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 microg) 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 microg 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-HT(3) 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-HT(3) receptors in conscious rats.
Nakade
Yukiomi
Y
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
Fukuda
Hiroyuki
H
Iwa
Masahiro
M
Tsukamoto
Kiyoshi
K
Yanagi
Hidenori
H
Yamamura
Takehira
T
Mantyh
Christopher
C
Pappas
Theodore N
TN
Takahashi
Toku
T
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002490:Central Nervous System / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000378:metabolism* / Q000503:physiopathology; D003243:Consciousness; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D005243:Feces / Q000737:chemistry; D005769:Gastrointestinal Motility / Q000187:drug effects; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D012149:Restraint, Physical / Q000009:adverse effects*; D012701:Serotonin / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D015167:Vagotomy, Truncal; D014630:Vagus Nerve / Q000378:metabolism* / Q000601:surgery; D000099052:CRF Receptor, Type 1
D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; C104416:astressin; D012701:Serotonin; D017294:Ondansetron; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D002211:Capsaicin