The possible involvement of pancreatic polypeptide in the paracrine regulation of human and rat adrenal cortex

Pancreatic polypeptide (PP) is a member of a family of 36-amino acid brain-gut peptides, including neuropeptide Y (NPY) and polypeptide YY (PYY) and acting through many subtypes of Y receptors belonging to the superfamily of the G protein-coupled receptors. PP was found to increase both glucocorticoid and cyclic-AMP production by dispersed rat and human adrenocortical cells in a concentration-dependent manner. Minimal and maximal effective concentrations were 10(-10) and 10(-8) M, respectively. The glucocorticoid secretagogue effect of 10(-8) M PP was blocked by the protein kinase A (PKA) unhibitor H-89, but not by the ACTH-receptor antagonist corticotropin-inhibiting peptide (CIP). Autoradiography showed the presence of [I-125]PP binding sites in the inner zones of rat and human adrenal cortex, which were not displaced by NPY, PYY, ACTH or CIP, Sizable amounts of PP-immunoreactivity were detected in the medulla of both rat and human adrenals (about 50-100 fmol/mg); this content may give rise, upon submaximal stimulation of PP release, to local intraadrenal concentrations of about 10(-8)/10(-7) M. Collectively, these findings allow us to draw the following conclusions: (i) PP stimulates glucocorticoid secretion, acting through specific receptors coupled with the adenylate cyclase/PKA-dependent signaling pathway; and (ii) PP could be included in that group of regulatory peptides, contained in adrenal medulla, which are able to control the secretory function of the cortex acting in a paracrine manner.