THE PROTECTIVE EFFECT OF 5-HT3 RECEPTOR ANTAGONIST IN THYROTROPIN-RELEASING-HORMONE INDUCED GASTRIC-LESIONS

The present study examined 1) oxidative stress and gastric lesions ind uced by thyrotropin releasing hormone (TRH) 2) The effect of a 5-hydro xytrypthamine3 (5-HT3) receptor antagonist, ICS 205930 on protective e ffect of calcitonin on gastric lesions produced by TRH. Calcitonin (5 mu g/10 mu l) was injected ICV 10 min before TRH (10 mu g/10 mu l, ICV ) injection or ICS 0.5 mg/kg, (IF) was given 60 min prior to calcitoni n or TRH to rats. Ulcer index, lipid peroxidation (LP) and glutathione (GSH) levels were quantified 3 h after TRH injection in the stomach, liver and brain. TRH caused mucosal lesions (UI: 10.0 +/- 2.0 mm) with out changing gastric GSH and LP. ICS did not alter the protective effe ct of calcitonin against TRH-induced lesions but attenuated TRH-induce d lesion formation. The oxidative effects of calcitonin or ICS were si milar to TRH but both drugs attenuated gastric lesion formation. Hence , oxidative changes in tissues studied are not directly involved in TR H-induced lesions. (C) 1997 Elsevier Science Inc.