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.
Miyata
K
K
Pharmacology Laboratories, Institute for Drug Discovery Research, Ibaraki, Japan.
Ito
H
H
Fukudo
S
S
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003672:Defecation / Q000187:drug effects / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D010078:Oxazines / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D012149:Restraint, Physical; D012702:Serotonin Antagonists / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology
D001562:Benzimidazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006727:Hormone Antagonists; D010078:Oxazines; D010446:Peptide Fragments; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C070671:azasetron; C071315:ramosetron; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)