INVESTIGATION ON THE MECHANISMS INVOLVED IN THE CENTRAL PROTECTIVE EFFECT OF AMYLIN ON GASTRIC-ULCERS IN RATS

1 The mechanisms involved in the protective effect of amylin (administ ered into the brain ventricle, i.c.v.) on gastric ulcers induced by th e oral administration of ethanol 50% (EtOH, 1 ml/rat) or indomethacin (indomethacin, 20 mg kg(-1), at a dosing volume of 5 mi) were investig ated in rats. 2 The possible involvement of endogenous nitric oxide (N O) in the beneficial effect of amylin against EtOH-induced ulcers was examined. The inhibitor of NO-synthesis, NG-nitro-L-arginine methyl ea ter (L-NAME, 70 mg kg(-1), s.c.) was injected 30 min before amylin (2. 2 mu g/rat, i.c.v.) followed by EtOH after a further 30 min. Rats were sacrified 1 h after EtOH. L-NAME completely removed the protective ef fect of amylin. 3 The interaction between amylin and gastric nonprotei n sulfhydryl groups was studied. The rats were treated with N-ethyl-ma leimide (NEM, 25 mg kg-L, s.c.) 30 min before amylin (2.2 mu g/rat, i. c.v.) followed by EtOH 30 min after or by indomethacin 5 min after amy lin. Rats were sacrified 1 h or 6 h respectively after EtOH or indomet hacin. NEM counteracted the protective effect of amylin against EtOH-i nduced ulcers but not against those provoked by indomethacin. 4 To det ermine whether amylin was able to promote ulcer healing, the peptide w as injected 5 min after EtOH or 1 h after indomethacin. In the case of EtOH, the beneficial effect of amylin was lost whereas it was still e ffective on indomethacin-induced ulcers. 5 The results indicate that: the mechanisms involved in the antiulcer effects of amylin are differe nt in these two types of gastric lesions probably because of the diffe rent etiopathology of various types of ulcers. Endogenous NO and nonpr otein sulfhydryl groups are involved in the mucosal protective effects of amylin on EtOH and not on indomethacin-induced ulcers. Furthermore the effectiveness of amylin against indomethacin-induced lesions when administered after the ulcerogenic process has started suggests that amylin is involved not only in the protection but also in the healing mechanisms in this type of ulcer.