Calcitonin gene-related peptide (CGRP), acting via CGRP type 1 receptors, inhibits potassium-stimulated aldosterone secretion and enhances basal catecholamine secretion from rat adrenal gland

Calcitonin gene-related peptide (CGRP) is a potent hypotensive peptide, tha t acts via two main subtypes of receptors, named CGRP I and CGRP2. CGRP bel ongs to a regulatory-peptide family, that includes adrenomedullin (ADM) who se aldosterone antisecretagogue and catecholamine secretagogue actions are well demonstrated. Quantitative autoradiography showed the presence of [I-1 25]CGRP binding sites in both rat adrenal zona glomerulosa (ZG) and medulla . Binding was displaced by the CGRP1-receptor antagonist CGRP(8-37), but no t by the CGRP2-receptor agonist [cys(Et)(2,7)]-alpha CGRP (CGRP2-A). CGRP c oncentration-dependently inhibited 10 mM-stimulated (but not basal) aldoste rone secretion from dispersed rat ZG cells, and enhanced basal catecholamin e secretion from rat adrenomedullary fragments. The responses to the maxima l effective concentration of CGRP (10(-8) M) were blocked by 10(-7) M CGRP( 8-37). CGRP2-A (10(-7) M) neither altered aldosterone response to 10 mM Knor enhanced basal catecholamine secretion. The conclusion is drawn that CG RP, like ADM, inhibits agonist-stimulated aldosterone secretion and stimula tes basal catecholamine release in the rat, exclusively acting via CGRP1 re ceptors.