Pancreastatin: molecular and immunocytochemical characterization of a novel peptide in porcine and human tissues

Abstract

Pancreastatin, a novel 49-amino acid peptide isolated from porcine pancreas, shows over 70% sequence homology to the central part of bovine and human chromogranin-A. Using an N-terminal and C-terminal synthetic peptide, we developed two sensitive and specific RIAs for the detection of pancreastatin-like immunoreactivity (PLI) in porcine and human tissue extracts. PLI was present throughout the gastrointestinal tract and in most endocrine and neuronal tissues. Highest concentrations were measured in the pituitary, adrenal gland, and pancreas (1200-4000 pmol/g), similar to the distribution of chromogranin-A. PLI was also detected in human endocrine tumors, with large quantities in some carcinoids (up to 14 nmol/g). HPLC revealed that extracts from porcine pituitary and pancreas contained small pancreastatin-like peptides, whereas in adrenal medulla large chromogranin-A-like molecular forms predominated. Human endocrine tumors showed a different pattern, with intermediate forms distinct from chromogranin-A and pancreastatin. Biochemical analysis was confirmed by immunocytochemistry localizing PLI in pancreatic islets, adrenal medulla, pituitary, duodenum, and human endocrine tumors. Pancreastatin is present in a variety of gastrointestinal, endocrine, and neuronal tissues and may represent a novel peptide of unknown physiological function, derived from chromogranin-A by proteolytic cleavage.