PROTECTION BY AMYLIN OF GASTRIC-EROSIONS INDUCED BY INDOMETHACIN OR ETHANOL IN RATS

1 The effect of amylin on gastric ulcers induced by oral administratio n of indomethacin (Indo, 20 mg kg(-1) at a dosing volume of 5 ml) or e thanol 50% (EtOH, 1 ml/rat) was investigated in conscious rats. 2 Amyl in given intracerebroventricularly (0.22, 0.66 and 2.2 mu g/rat, i.c.v .) demonstrated a dose-dependent cytoprotective effect against both In do and EtOH-induced ulcers. In contrast, amylin, given subcutaneously at doses effective in inhibiting acid gastric secretion (2.5, 10 and 4 0 mu g kg(-1), s.c.), did not show any cytoprotective effect. 3 The in teraction between amylin and endogenous nitric oxide (NO) in the maint enance of gastric mucosal integrity was investigated by pretreating th e rats with a selective inhibitor of NO-synthesis, N-G-nitro-L-arginin e methyl ester (L-NAME, 25 and 70 mg kg(-1), s.c.). Administration of L-NAME to rats did not significantly increase the degree of the Indo-i nduced ulcer index and was not able to remove the protective effect of amylin on Indo-induced ulcers, thus excluding a role for endogenous N O in mediating the protective effect of this peptide. 4 To determine w hether the cytoprotective effect of amylin was mediated by endogenous prostaglandins, we studied the effect of amylin (2.2 mu g/rat, i.c.v.) on EtOH- induced ulcers in rats pretreated with Indo (10 mg kg(-1), s .c.) to inhibit prostanoid biosynthesis; Indo was injected 30 min befo re amylin and EtOH after a further 30 min. Pretreatment with Indo did not significantly increase the ulcer index induced by EtOH but counter acted the ability of amylin to prevent the ulcer formation. 5 These fi ndings suggest that amylin exerts a gastroprotective activity that is not strictly related to inhibition of acid gastric secretion and can b e partly explained through a prostaglandin-dependent mechanism mediate d by receptors for the peptide in the brain. Amylin might be considere d as a new brain-gut peptide.