Involvement of the 5-HT3 receptor in CRH-induce defecation in rats.

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 (i.c.v.) injection of CRH (1, 3, and 10 micrograms/rat) dose dependently increased the number of stools excreted in rats, whereas intravenous (i.v.) injection of up to 100 micrograms/kg CRH did not affect defecation. alpha-Helical CRH-(9-41) and 5-HT3 receptor antagonists ramosetron and azasetron inhibited CRH (10 micrograms i.c.v.)-induced defecation in a dose-dependent manner with ED50 values of 4.3 micrograms/kg i.v., 3.8 micrograms/kg p.o., and 70.4 micrograms/kg p.o., respectively. alpha-Helical CRH-(9-41) also inhibited CRH-induced defecation by i.c.v. injection with an ED50 value of 0.078 microgram/rat. In contrast, ramosetron and azasetron injected i.c.v. 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 micrograms/kg i.v., 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.