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Structure-activity relationship of the chicken calcitonin gene-related peptide (cCGRP) was investigated and compared with human-alpha-CGRP (hCGRP) and rat CGRP (rCGRP) in the perfused mesenteric vascular beds of rats. In precontracted mesenteric vascular beds, cCGRP, hCGRP and rCGRP produced a concentration-dependent vasodilation. The vasodilator activities of cCGRP and rCGRP were equipotent and more potent than that of hCGRP. (Ala2,7)cCGRP and (Des-1-Ala)-alpha-deamino cCGRP were 100- and 10-fold less potent than cCGRP, respectively. However, cCGRP[1-36] reduced vasodilator activity. The cCGRP[8-37] produced a vasoconstriction. Both cCGRP[8-37] and hCGRP[8-37] caused parallel shifts of the concentration-response curves of rCGRP to the right, but both peptides did not affect the maximum response and vasodilator responses to isoproterenol, these peptides being equipotent antagonists (pA2 values: 7.6 and 7.4). In rat brain membrane preparations, cCGRP and its fragments and analogues, except for cCGRP[1-36], competed for specific binding sites with [125I]-hCGRP. These results suggest that cCGRP has a potent vasodilator activity for which the disulfide bridge at position 2 and 7 of cCGRP is an important site and that position 37 is necessary for the binding of the peptide to the receptor. Also, cCGRP[8-37] is a competitive CGRP-receptor antagonist.

Structure-Activity Study of Chicken Calcitonin Gene-Related Peptide (CGRP) on Vasorelaxation in Rat Mesenteric Resistance Vessels.