PANCREASTATIN ACTION IN THE LIVER - DUAL COUPLING TO DIFFERENT G-PROTEINS

Pancreastatin is a 49 amino acid peptide first isolated, purified and characterized from porcine pancreas. Its biological activity in differ ent tissues can be assigned to the C-terminal part of the molecule. Pa ncreastatin has a prohormonal precursor, chromogranin A, which is a gl ycoprotein present in neuroendocrine cells, including the endocrine pa ncreas. We have been interested in pancreastatin action in the liver. We found that pancreastatin has a glycogenolytic effect in the hepatoc yte both in vivo and in vitro. We then studied and characterized the s pecific pancreastatin receptor in the rat liver plasma membrane, as we ll as the specific signal transduction. This receptor appears to be co upled to two different G proteins. A pertussis toxin-insensitive G pro teins leads to the activation of phospholipase C, and therefore mediat es the glycogenolytic effect in the liver by increasing cytoplasmic fr ee calcium and stimulating protein kinase C. The role of cyclic GMP in the action of pancreastatin is not known yet, although it seems to re gulate negatively the activation of phospholipase C. The precise mecha nism by which pancreastatin stimulates guanylate cyclase activity rema ins to be studied.