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

Abstract

Pancreatic polypeptide (PP) is a member of a family of 36-amino acid braingut 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 [125I]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.