Pancreatic polypeptide stimulates rat adrenal glucocorticoid secretion by activating the adenylate cyclase-dependent signaling pathway.

Pancreatic polypeptide (PP) concentration-dependently raised basal corticosterone and cyclic-AMP production of dispersed rat zona fasciculata/reticularis adrenocortical cells, maximal effective concentration being 10(-7) M. 10(-7) M PP also significantly enhanced submaximally (10[-12]/10[-11] M), but not maximally (10[-9]/10[-8] M) ACTH-stimulated corticosterone and cyclic-AMP release. Corticosterone responses to PP were abolished by the specific protein kinase A (PKA) antagonist H-89 (10[-5] M). The selective ACTH-receptor antagonist corticotropin-inhibiting peptide (10[-6] M) annulled corticosterone response to 10(-9) M ACTH, but not to 10(-7) M PP. Collectively, our present findings indicate that PP stimulates glucocorticoid secretion of rat adrenal glands, acting through specific receptors coupled, like those of ACTH, with the adenylate cyclase/PKA-dependent signaling pathway.