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Am J Physiol Gastrointest Liver Physiol 274: G827-G831, 1998;
0193-1857/98 $5.00
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Vol. 274, Issue 5, G827-G831, May 1998

Involvement of the 5-HT3 receptor in CRH-induced defecation in rats

Keiji Miyata1, Hiroyuki Ito1, and Shin Fukudo2

1 Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical, Tsukuba, Ibaraki 305; and 2 Department of Psychosomatic Medicine, Tohoku University School of Medicine, Aoba-ku, Sendai 980, Japan

We evaluated the possibility that serotonin (5-HT) mediates defecation induced by corticotropin-releasing hormone (CRH) exogenously administered or released from the central nervous system by stress via the 5-HT3 receptor in rats. Intracerebroventricular (ICV) injection of CRH (1, 3, and 10 µg/rat) dose dependently increased the number of stools excreted in rats, whereas intravenous (IV) injection of up to 100 µg/kg CRH did not affect defecation. alpha -Helical CRH-(9---41) and 5-HT3 receptor antagonists ramosetron and azasetron inhibited CRH (10 µg icv)-induced defecation in a dose-dependent manner with ED50 values of 4.3 µg/kg iv, 3.8 µg/kg po, and 70.4 µg/kg po, respectively. alpha -Helical CRH-(9---41) also inhibited CRH-induced defecation by ICV injection with an ED50 value of 0.078 µg/rat. In contrast, ramosetron and azasetron injectied ICV had no effect on CRH-induced defecation. alpha -Helical CRH-(9---41), ramosetron, and azasetron reduced defecation caused by restraint stress with ED50 values of 0.32, 3.6, and 19.7 µg/kg iv, respectively. These results indicate that CRH exogenously administered or released from the central nervous system by stress peripherally promotes the release of 5-HT, which in turn stimulates defecation through the 5-HT3 receptor.

serotonin3 receptor; corticotropin-releasing hormone; ramosetron; azasetron


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