The delta opioid receptor 1 is expressed by proliferating bile ductules in rats with cholestasis: Implications for the study of liver regeneration and malignant transformation of biliary epithelium

Abstract

In sharp contrast with the normal adult liver, the fetal human and rat livers and the liver of rats with cholestasis secondary to bile duct resection express the preproenkephalin mRNA, which codes for the endogenous opioid peptide Met-enkephalin. Furthermore, Met-enkephalin immunoreactivity is detected in hepatocytes and in proliferating bile ductules in the cholestatic rat liver. These data suggest that in cholestasis endogenous opioids may have a local effect in the cholestatic liver. As endogenous opioids exert their effect by binding to opioid receptors, the presence of opioid receptors in the cholestatic livers would support the hypothesis that Met-enkephalin plays a role in situ. Preliminary data presented in this manuscript reveals the expression of the delta opioid receptor in the liver of rats with cholestasis. This finding suggests that there is a scenario in which Met-enkephalin can bind to opioid receptors in the liver in cholestasis to exert a local effect. In vivo studies in this model of cholestasis with the use of opioid agonist and antagonist will shed light on the possible role of opioidergic regulation of liver regeneration. Studies on the effect of opiate antagonists on the evolution of cholestasis in this animal model may provide insight into the mechanisms of liver regeneration. In addition, as some conditions associated with cholestasis and bile ductular proliferation can be complicated by malignancy, the expression of the delta opioid receptor in malignant tumors of the biliary tree merits research.