DIVERSE INTERACTIONS OF CALCITONIN-GENE-RELATED PEPTIDE AND NITRIC-OXIDE IN THE GASTRIC AND CUTANEOUS MICROCIRCULATION

Calcitonin gene related peptide (CORP) is the major mediator of affere nt nerve mediated vasodilatation in the gastric mucosa and skin of the rat. Since receptors for CORP occur on both the vascular endothelium and smooth muscle, it is conceivable that the vascular actions of CGRP involve multiple mechanisms. The vasodilator effect of rat CGRP-alpha in the rat gastric mucosa is indeed inhibited by blockade of nitric o xide (NO) synthesis, as is the gastric mucosal hyperemia in response t o gastric acid challenge, which is mediated by CORP release from affer ent nerve fibres. In contrast, the vasodilator response to rat CGRP-al pha in the rat hind paw and the CGRP-mediated vasodilatation evoked by antidromic stimulation of afferent nerve fibres do not depend on the formation of NO. These data indicate that NO plays regionally differen t roles in the local vasodilator action of CGRP. NO is a secondary vas orelaxant messenger of CGRP in the gastric, but not in the cutaneous, microcirculation. However, this L-arginine-derived autacoid may have a role in the irritant-induced CGRP release from afferent vasodilator f ibres in the skin.