The role of sensory neurons in the antiulcer effect of centrally injected amylin in rat

Central administration of amylin (2.2 microg/rat, i.c.v.) reduces (from a minimum of 67% to 83%) indomethacin (Indo, 20 mg Kg(-1), orally) induced ulcers in rats. The anti-ulcer effect of the peptide is not removed by the administration of prokinetic drugs like domperidone or neostigmine but it is reduced by 35% in rats treated with capsaicin or with the CGRP antagonist, CGRP(8-37). These data indicate that amylin gastroprotection involves capsaicin-sensitive nerve fiber leading to CGRP-dependent gastric vasodilatory effect. Additional mechanisms could involve noradrenergic alpha(2) receptors as the peptide gastroprotective activity is reduced from 67% to 20% by the alpha(2) antagonist yohimbine.