Receptors mediating CGRP-induced relaxation in the rat isolated thoracic aorta and porcine isolated coronary artery differentiated by h alpha CGRP(8-37)

1 Receptors mediating CGRP-induced vasorelaxation were investigated in rat thoracic aorta and porcine left anterior descending (LAD) coronary artery a nd anterior interventricular artery (AIA), using CGRP agonists, homologues and the antagonist h alpha CGRP(8-37). 2 In the endothelium-intact rat aorta, h alpha CGRP, h beta CGRP, rat beta CGRP and human adrenomedullin caused relaxation with similar potencies. Com pared with h alpha CGRP, rat amylin was about 25 fold less potent, while [C ys(ACM(2.7))] h alpha CGRP and salmon calcitonin were at least 1000 fold we aker. 3 H alpha CGRP(8-37) (up to 10(-5) M) did not antagonize responses to h alp ha CGRP, h beta CGRP or rat beta CGRP (apparent pK(B) < 5). Peptidase inhib itors did not increase either the effect of her CGRP or [Cys(ACM,(2.7))] h alpha CGRP, while h alpha CGRP(8-37) remained inactive. Endothelium-depende nt relaxation produced by ha CGRP was accompanied by increases in cyclic AM P and cyclic GMP, that were not inhibited by her CGRP(8-37) (10(-5) M). 4 In porcine LAD and AIA, h alpha CGRP produced relaxation in an endotheliu m-independent manner. H alpha CGRP(8-37) competitively antagonized h alpha CGRP responses (pA(2) 6.3 and 6.7 (Schild slope 0.9 +/- 0.1, each), in LAD and AIA, respectively). In LAD artery, ha CGRP-induced relaxation was accom panied by increases in cyclic AMP that were inhibited by h alpha CGRP(8-37) (10(-7)-10(-5) M). 5 In conclusion, the antagonist affinity for h alpha CGRP(8-37) in porcine coronary artery is consistent with a CGRP(1) receptor, while the lack of h alpha CGRP(8-37) antagonism in rat aorta could suggest either a CGRP recept or different from CGRP(1) and CGRP(2) type, or a non-CGRP receptor.