HEPATIC CONCENTRATIONS OF PROENKEPHALIN-DERIVED OPIOIDS ARE INCREASEDIN A RAT MODEL OF CHOLESTASIS

The liver of adult rats with cholestasis secondary to bile duct resect ion has been shown to express the proenkephalin gene and, by immunohis tochemical stains, to contain met-enkephalin. To further study hepatic opioids in cholestasis, concentrations of proenkephalin-derived endog enous opioids were measured in a rat model of cholestasis by the use o f radioimmunoassays. The specificity of the immunoreactivity detected by the assays was confirmed by high performance liquid chromatography (HPLC). In adult male rats with cholestasis due to BDR, the concentrat ions of three proenkephalin-derived opioid peptides were increased. Sp ecifically, the mean hepatic concentrations of met-enkephalin, Met-Enk -Arg(6)-Phe(7) and leu-enkephalin were 2.5 (p<0.005), 2.1 (p<0.005) an d 2.5 (p<0.01) fold higher than the corresponding mean for controls. T hese findings provide further independent evidence that opioid peptide s accumulate in the liver in a model of cholestasis and are consistent with de novo synthesis of opioid peptides occurring in the cholestati c liver. This phenomenon may have relevance to the altered function of the opioid system in cholestasis and to the role of the liver as a ne uroendocrine organ.