UP-REGULATION OF ESCHERICHIA-COLI HEAT-STABLE ENTEROTOXIN RECEPTOR INREGENERATING RAT-LIVER

Guanylate cyclase C (GC-C) is a transmembrane protein that serves as a receptor for the recently characterized endogenous ligand guanylin an d for Escherichia coli heat-stable toxin (STa). Binding of either guan ylin or STa to intestinal GC-C results in net chloride secretion. Alth ough GC-C is expressed in the rat intestine throughout life, its expre ssion in the rat liver has previously been shown to occur only during the perinatal period. As a step toward elucidating the role of this re ceptor in the liver, we tested the hypothesis that GC-C mRNA expressio n could be induced in the adult rat liver following 1) partial hepatec tomy, a stimulus for hepatocyte proliferation; 2) intraperitoneal carb on tetrachloride injection, a model of hepatocyte regeneration in the presence of inflammatory changes; and 3) subcutaneous turpentine injec tion, which generates an acute phase response without hepatocyte proli feration. 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 as sociation with an acute phase reaction. Coordinate with the expression of GC-C mRNA, there was upregulation of radiolabeled STa binding to l iver plasma membranes prepared from turpentine-treated rats. Maximal e xpression of GC-C occurred in preparations enriched for the canalicula r domain. Although the function of GC-C in the liver is unknown, local ization 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.