Pharmacologic study of C-terminal fragments of frog skin calcitonin gene-related peptide

The calcitonin gene-related peptide from the skin of the frog Phyllomedusa bicolor (pbCGRP) is a 37-residue neuropeptide that differs from human α CGRP (hαCGRP) at 16 positions. The affinities of the C-terminal fragments of pbCGRP and hαCGRP were evaluated in SK-N-MC cells: pbCGRP8-37 (Ki = 0.2 nM) and pbCGRP27-37 (Ki = 95 nM) were, respectively, 3 times and 20 times more potent than the human fragments hαCGRP8-37 and hαCGRP27-37. Their antagonistic potencies were measured in SK-N-MC and Col 29 cells, and the rat vas deferens. pbCGRP8-37 inhibited the hαCGRP-stimulated production of cAMP by SK-N-MC and Col 29 cells 3 to 4 times more strongly than hαCGRP8-37. Thus pbCGRP8-37 is the most potent CGRP-1 competitive antagonist of all the natural sequences reported to date. pbCGRP27-37 was also as potent as [D31, A34, F35] hαCGRP27-37, a prototypic antagonist analog derived from structure-activity relationship studies of hαCGRP8-37.