[Effect of Y-25130, a selective 5-HT3 receptor antagonist, on the intestinal fluid secretion in rats].
We studied the effect of Y-25130 on the intestinal fluid secretion induced by 5-HT and cholera toxin in rats. 1) Net fluid secretion was increased dose-dependently by intramesenteric artery infusion of 5-HT (1-10 micrograms/min). 2) Y-25130 (0.01-1 mg/kg, i.v.) inhibited the net fluid secretion induced by 5-HT (3 micrograms/min). Granisetron and ondansetron also inhibited the net fluid secretion induced by 5-HT. 3) Methysergide did not inhibit the fluid secretion, and neither atropine nor tetrodotoxin inhibited it. 4) Cholera toxin (1-10 micrograms/2 ml into jejunal loops) caused profuse net fluid secretion. 5) Y-25130 (1 mg/kg, i.v.) inhibited the net fluid secretion induced by cholera toxin (3 micrograms/2 ml). Granisetron was inhibitory and ondansetron tended to inhibit the cholera toxin-induced secretion. These results suggest that 5-HT may increase the net fluid secretion through 5-HT3 receptors, and cholera toxin-induced fluid secretion may be at least partially mediated by 5-HT3 receptors. It is expected that Y-25130 may be useful for treating secretory diarrhea in humans.
Ooe
M
M
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Asano
K
K
Haga
K
K
Setoguchi
M
M
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002772:Cholera Toxin / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D007419:Intestinal Secretions / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010078:Oxazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists
D000932:Antiemetics; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010078:Oxazines; D012702:Serotonin Antagonists; C070671:azasetron; D002772:Cholera Toxin