guanylin and Carbon-Tetrachloride-Poisoning

Guanylate cyclase C (GC-C) is a transmembrane protein that serves as a receptor for the recently characterized endogenous ligand guanylin and for Escherichia coli heat-stable toxin (STa). Binding of either guanylin or STa to intestinal GC-C results in net chloride secretion. Although GC-C is expressed in the rat intestine throughout life, its expression in the rat liver has previously been shown to occur only during the perinatal period. As a step toward elucidating the role of this receptor in the liver, we tested the hypothesis that GC-C mRNA expression could be induced in the adult rat liver following 1) partial hepatectomy, a stimulus for hepatocyte proliferation; 2) intraperitoneal carbon tetrachloride injection, a model of hepatocyte regeneration in the presence of inflammatory changes; and 3) subcutaneous turpentine injection, which generates an acute phase response without hepatocyte proliferation. We demonstrated expression of GC-C mRNA in the regenerating rat liver following either partial hepatectomy or CCl4-induced hepatic necrosis. We have also shown that GC-C mRNA expression occurred in association with an acute phase reaction. Coordinate with the expression of GC-C mRNA, there was upregulation of radiolabeled STa binding to liver plasma membranes prepared from turpentine-treated rats. Maximal expression of GC-C occurred in preparations enriched for the canalicular domain. Although the function of GC-C in the liver is unknown, localization to the canalicular domain would be consistent with a role for GC-C in hepatic chloride secretion, especially in the perinatal liver and during hepatocyte regeneration.

Topics: Animals; Bacterial Toxins; Blotting, Southern; Carbon Tetrachloride Poisoning; Cell Division; Cell Membrane; DNA Probes; Enterotoxins; Escherichia coli; Escherichia coli Proteins; Gastrointestinal Hormones; Gene Expression; Guanylate Cyclase; Hepatectomy; Ileum; Kinetics; Liver; Liver Regeneration; Male; Natriuretic Peptides; Oligonucleotide Probes; Peptides; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; Receptors, Enterotoxin; Receptors, Guanylate Cyclase-Coupled; Receptors, Peptide; RNA, Messenger; Time Factors; Turpentine; Up-Regulation