STIMULATION OF PROHORMONE CONVERTASE-1 MESSENGER-RNA EXPRESSION BY 2ND-MESSENGER SIGNALING SYSTEMS

The purpose of this study was to investigate the effects of activation of various second messenger signaling systems on gene expression (ie. mRNA levels) of a peptide hormone processing enzyme called prohormone convertase-1 (PC-1, also called PC-3) in a human pancreatic carcinoid cell line (BON) that expresses several endocrine peptides (chromogran in A, pancreastatin, neurotensin). Pharmacologic activation of adenyla te cyclase-cAMP, protein kinase-C and Ca2+ mobilization pathways incre ased PC-1 mRNA levels and neurotensin secretion. Elevations in PC-1 mR NA levels were dose and time-related. Secretagogue-induced cellular de pletion of neurotensin was followed by a replenishment of cellular neu rotensin stores and an upregulation of PC-1 mRNA levels. Together, the se data indicate that PC-1 mRNA expression is increased with peptide s ecretion and coordinated with maintenance of cellular stores of peptid es. (C) 1998 Academic Press.