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.