Characterization of the receptor mediating the effect of calcitonin gene-related peptide in the frog adrenal gland

We have recently reported the presence of calcitonin gene-related peptide (CGRP)-containing nerve fibers in the frog adrenal gland and we have shown that CGRP is a potent stimulator of corticosterone and aldosterone secretion by adrenocortical cells. The aim of the present study was to characterize the type of receptors mediating the effect of CGRP in the frog adrenal gland. Amylin and adrenomedullin, two members of the CGRP family, induced a weak stimulation of corticosterone and aldosterone secretion from perifused frog adrenal slices, In contrast, salmon and human calcitonin had no effect on corticosteroid secretion. Administration of the type-1 CGRP receptor antagonists human CGRP-(8-37) and human CGRP-(19-37) did not significantly affect the secretory response induced by frog CGRP. Concurrently, the type-2 CGRP receptor agonist [acetamidomethyl-Cys(2,7)]human CGRP ([Cys(ACM)(2,7)]human CGRP) provoked a dose-dependent stimulation of corticosterone and aldosterone secretion (EC(50) = 1.6 X 10(-7) M). Both frog CGRP and [Cys(ACM)(2,7)]human CGRP induced a significant increase in cAMP production by frog adrenal tissue. These data indicate that, in the frog adrenal gland, the stimulatory effect of CGRP is mediated through activation of a type-2 CGRP receptor positively coupled to adenylyl cyclase.