title: Endogenous opioids accumulate in plasma in a rat model of acute cholestasis.
abstract: 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.
authors.affiliation: Liver Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: M G
authors.initials: MG
authors.lastname: Swain
authors.forename: R B
authors.initials: RB
authors.lastname: Rothman
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Vergalla
authors.forename: N V
authors.initials: NV
authors.lastname: Bergasa
authors.forename: E A
authors.initials: EA
authors.lastname: Jones
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000097:blood; D000818:Animals; D002779:Cholestasis / Q000097:blood*; D004195:Disease Models, Animal; D004723:Endorphins / Q000097:blood*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004744:Enkephalin, Methionine / Q000097:blood; D004745:Enkephalins / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D004723:Endorphins; D004745:Enkephalins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004744:Enkephalin, Methionine; D000626:Aminopeptidases