CHARACTERIZATION OF CALCITONIN GENE-RELATED PEPTIDE (CGRP) RECEPTORS IN GUINEA-PIG BASILAR ARTERY

The vasomotor effects of calcitonin gene-related peptide (CGRP) analogs have been studied in circular segments of guinea pig basilar artery in vitro. Five CGRP agonists induced concentration-dependent relaxations of pre-contracted vessels with the following order of potency: alpha-rCGRP greater-than-or-equal beta-rCGRP greater-than-or-equal-to alpha-hCGRP > beta-hCGRP > [Tyr0]CGRP with maximum responses between 80 and 87%. The magnitude of responses to calcitonin was low (12%) but with the same potency as the CGRP analogs. hCGRP(8-37) (10(-6)M), a CGRP antagonist, induced a parallel shift of alpha-rCGRP- and alpha-hCGRP-induced relaxations but not of beta-rCGRP and beta-hCGRP. Another putative antagonist [Tyr0]CGRP28-37 (10(-6)M) had no antagonistic effect on dilator responses to the CGRP agonists. The results suggests two types of CGRP responses in the guinea pig basilar artery: alpha-CGRP induced relaxation is blocked by the antagonist hCGRP(8-37), while the equally strong dilator response to beta-CGRP is not antagonized. It is therefore possible that the guinea pig basilar artery is equipped with CGRP-1 receptors sensitive to hCGRP(8-37) and CGRP-2 receptors being sensitive to beta-CGRP but not antagonized by hCGRP(8-37).