Endogenous opioids accumulate in plasma in a rat model of acute cholestasis

Gastroenterology. 1992 Aug;103(2):630-5. doi: 10.1016/0016-5085(92)90857-u.


To obtain data on the degree to which the opioid system is changed in cholestasis, endogenous opioid activity in plasma of rats with acute cholestasis was determined 5 days after bile duct resection. Total plasma opioid activity was determined using a radioreceptor technique that measured the displacement of the opiate receptor ligand [3H]-DAMGO from lysed synaptosomal fractions of normal rat brain. Plasma total opioid activity was threefold greater in bile duct-resected rats than in sham-operated and unoperated controls (P less than or equal to 0.05). Plasma levels of the individual endogenous opioid, methionine-enkephalin, were determined using a sensitive radioimmunoassay, and the specificity of the assay was confirmed using high-performance liquid chromatography. In cholestatic rats, plasma methionine-enkephalin levels were more than six-fold greater than in sham-operated controls (P less than or equal to 0.001) and more than 17-fold greater than in unoperated controls (P less than or equal to 0.001). However, plasma methionine-enkephalin levels accounted for less than 5% of total plasma opioid activity after bile duct resection. Plasma methionine-enkephalin levels in both cholestatic plasma and plasma from sham-operated animals were stable when incubated in vitro despite the presence of undiminished activity of the major enkephalin-degrading enzymes. Thus, protection of methionine-enkephalin from degradation may be a factor contributing to the elevated plasma levels of methionine-enkephalin found in cholestasis. The magnitude of the increase in plasma endogenous opioid activity in bile duct-resected rats provides support for the hypothesis that endogenous opioids contribute to the pathophysiology of cholestasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Amino Acid Sequence
  • Aminopeptidases / blood
  • Animals
  • Cholestasis / blood*
  • Disease Models, Animal
  • Endorphins / blood*
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalin, Methionine / blood
  • Enkephalins / metabolism
  • Male
  • Molecular Sequence Data
  • Rats
  • Rats, Inbred Strains


  • Endorphins
  • Enkephalins
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalin, Methionine
  • Aminopeptidases