G protein-mediated signal transduction is affected in primary biliary cirrhosis

Abstract

Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by severe intraepatic cholestasis. Pruritus often occurs during the course of the illness. We designed a study aimed at assessing whether pruritus is associated with dysfunction of signal transduction. Seventeen female patients affected by PBC were enrolled into the study and divided in two groups according to severity of liver disease. Leukocytes were isolated from peripheral blood and Gi, Go and Gs protein expressions were evaluated by western blotting, while G protein function was assessed by measuring cyclic adenosine phosphate formation. The expression of all types of G proteins was increased in leukocytes of PBC patients. The basal adenylate activity was significally higher than control in patients with less severe liver disease, while it was lower than normal in those with severe liver disease. Incubation of patient leukocytes with guanosine triphosphate-gamma-S and Gs protein activators failed to enhance cAMP production, while N-formyl-met-leu-phe was more effective in reducing cAMP production. The expression of all G proteins was non-selectively increased in PBC leukocytes, while adenylate cyclase activity was significantly modified. However, the observed changes in G proteins expression and in adenylate cyclase activity are not related to the presence of pruritus.