THE HEAT-STABLE ENTEROTOXIN-GUANYLIN RECEPTOR IS EXPRESSED IN RAT HEPATOCYTES AND IN A RAT HEPATOMA (H-35) CELL-LINE

Background/Aims: Guanylyl cyclase C (GC-C) is an intestinal transmembr ane receptor which binds both guanylin, an endogenous ligand, and Esch erichia coli heat-stable enterotoxin (STa) resulting in 5'-cyclic guan osine monophosphate (cGMP) accumulation and chloride secretion. In the adult rat, there is a high basal level of GC-C expression in the inte stine, but not in the liver. Increased expression of GC-C in the rat l iver has been demonstrated during the perinatal period as well as with liver regeneration and during an acute phase response. The aim of thi s study was to identify and utilize cell culture models to further cha racterize the expression of GC-C in the liver. Methods: STa binding, S Ta-stimulated cGMP accumulation, and GC-C RNA expression by Northern a nalysis were determined in primary cultures of rat hepatocytes and H-3 5 cells, a rat hepatoma cell line, following treatment with dexamethas one and/or interleukin-6 (IL-6). Results: In rat hepatocytes treated w ith the combination of dexamethasone and IL-6, there was an increase i n STa binding, STa-stimulated cGMP accumulation, and GC-C RNA expressi on as compared to untreated cells. In H-35 cells treated with dexameth asone alone, there was an increase in STa binding, STa-stimulated cGMP accumulation, and GC-C RNA expression as compared to untreated cells. Conclusion: Primary cultures of rat hepatocytes and H-35 cells can be utilized to further study upregulation of GC-C in the hepatocyte. The expression of this receptor in hepatocytes, combined with the recent demonstration of circulating guanylin, is consistent with a functional role for GC-C in the liver.