AJP - Gastrointestinal and Liver Physiology, Vol 268, Issue 2 346-G354, Copyright © 1995 by American Physiological Society
Cholestasis is associated with preproenkephalin mRNA expression in the adult rat liver
N. V. Bergasa, S. L. Sabol, W. S. Young 3rd, D. E. Kleiner and E. A. Jones
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Cholestatic liver disease is associated with clinical and experimental
findings consistent with increased opioidergic neuromodulation, increased
plasma total opioid activity, and elevated plasma enkephalin
concentrations. In contrast to the normal adult rat liver, preproenkephalin
mRNA was detected by Northern blotting in livers of adult rats with
cholestasis due to bile duct resection and not in the sham-resected
controls. Preprodynorphin mRNA was not detected in livers of either group,
while preproopiomelanocortin mRNA was found in very low levels in both
groups. Preproenkephalin mRNA was not expressed in the livers of rats with
acute hepatocellular necrosis induced by thioacetamide. Hybridization
histochemistry of cholestatic livers demonstrated the presence of
preproenkephalin mRNA primarily over cells in the periportal areas, some of
which appeared to be proliferating bile ductular cells. Immunohistochemical
staining of cholestatic liver indicated the production of at least
Met-enkephalin in association with preproenkephalin gene expression. These
findings suggest that the liver itself, by synthesizing enkephalins,
contributes directly to the abnormalities of the opioid system reported in
cholestasis.
