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 different tissues can be assigned to the C-terminal part of the molecule. Pancreastatin has a prohormonal precursor, chromogranin A, which is a glycoprotein present in neuroendocrine cells, including the endocrine pancreas. We have been interested in pancreastatin action in the liver. We found that pancreastatin has a glycogenolytic effect in the hepatocyte both in vivo and in vitro. We then studied and characterized the specific pancreastatin receptor in the rat liver plasma membrane, as well as the specific signal transduction. This receptor appears to be coupled to two different G proteins. A pertussis toxin-insensitive G proteins leads to the activation of phospholipase C, and therefore mediates the glycogenolytic effect in the liver by increasing cytoplasmic free calcium and stimulating protein kinase C. The role of cyclic GMP in the action of pancreastatin is not known yet, although it seems to regulate negatively the activation of phospholipase C. The precise mechanism by which pancreastatin stimulates guanylate cyclase activity remains to be studied.
Sánchez-Margalet
V
V
Departamento De Bioquímica Médica y Biología Molecular, Facultad De Medicina, Universidad De Sevilla, Hospital Universitario Virgen Macarena, Spain.
Lucas
M
M
Goberna
R
R
D000818:Animals; D002147:Calmodulin / Q000502:physiology; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D006152:Cyclic GMP / Q000502:physiology; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology*; D006003:Glycogen / Q000096:biosynthesis; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000502:physiology*; D008954:Models, Biological; D010187:Pancreatic Hormones / Q000502:physiology*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013552:Swine
D002147:Calmodulin; D053379:Chromogranin A; D002864:Chromogranins; D010187:Pancreatic Hormones; D011498:Protein Precursors; D011964:Receptors, Gastrointestinal Hormone; C029438:receptors, pancreatic polypeptide-specific; C050836:pancreastatin; D006003:Glycogen; D010727:Phosphoric Diester Hydrolases; D019204:GTP-Binding Proteins; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D006162:Guanylate Cyclase; D006152:Cyclic GMP