CHARACTERIZATION OF THE CGRP RECEPTOR AND MECHANISMS OF ACTION IN RATMESENTERIC SMALL ARTERIES

Rat alpha-calcitonin gene-related peptide-induced concentration-depend ent (100 pM - 10 nM) relaxations in rat mesenteric small arteries (i.d . approximate to 220 mu m) contracted with noradrenaline, prostaglandi n F-2 alpha or K+, however, the maximal relaxation depended on the pre contractile stimulus, being highest (95%) in arteries contracted with PGF(2 alpha) and lowest (51%) in arteries contracted with 125 mM K+. T he relaxation was inhibited between 10 pM and 1 nM by removal of the e ndothelium, but was not antagonized by glibenclamide (1 mu M), tetraet hylammonium (30 mM), apamine (0.3 mu M) and 4-aminopyridine (3 mM). Th e concentration-response curve to rat alpha-CGRP and human beta-CGRP w as shifted to the right in the presence of 1 mu M human alpha-CGRP(8-3 7) indicating a receptor affinity, -log(K-B[M]), equal to 7.2 and 7.0, respectively. It is concluded than the relaxation induced by CGRP dep ends minimally on the endothelium and K+-channel opening is not a prin cipal process in the relaxing effect of CGRP, thus a third mechanism m ust mediate the relaxation in these vessels. The main CGRP receptor ty pe mediating relaxation in rat mesenteric small arteries belongs to th e CGRP, subtype.