Potentiating interactions between medullary serotonin and thyrotropin-releasing hormone-induced gastric erosions in rats.
The central interaction between 5-HT and exogenous and endogenous thyrotropin-releasing hormone (TRH)-induced gastric lesions was investigated in conscious rats. Intracisternal injection (i.c.) of the TRH analog, RX 77368, (2.5 nmol) in indomethacin (2 mg/kg, i.p.)-treated rats produced 1.4 +/- 0.1% of gastric corpus mucosal lesions which were aggravated by 30 and 208% by simultaneous i.c. injection 5-HT at 10 and 100 nmol, respectively, whereas i.v. 5-HT (100 nmol) had no effect. The 5-HT2/1c antagonist, ketanserin, given i.c. at 10 or 100 nmol reduced by 44 and 76%, respectively, cold restraint stress-induced 3.4 +/- 0.6% gastric lesions in indomethacin-pretreated rats whereas, when given i.v. (100 nmol), it was inactive. Ketanserin or 5-HT (100 nmol, i.c.) alone did not modify the gastric mucosa. The present data suggest a potentiating interaction between endogenous 5-HT and TRH which has implication in the understanding of medullary mechanisms involved in gastric lesion formation induced by cold restraint.
Yoneda
M
M
CURE/Digestive Disease Center, VA Wadsworth Medical Center, Los Angeles, CA 90073.
Taché
Y
Y
D000818:Animals; D003080:Cold Temperature; D007213:Indomethacin; D007267:Injections; D007275:Injections, Intravenous; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology; D013315:Stress, Psychological / Q000150:complications; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives
D012701:Serotonin; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D007650:Ketanserin; D011761:Pyrrolidonecarboxylic Acid; D007213:Indomethacin