Endogenous opioids accumulate in plasma in a rat model of acute cholestasis.
1Liver Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Gastroenterology
|August 1, 1992
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Summary
Cholestasis significantly elevates plasma opioid activity and methionine-enkephalin levels in rats, suggesting endogenous opioids play a role in the condition. Protection from degradation may contribute to these increased opioid levels.
Area of Science:
- Biochemistry
- Physiology
- Pharmacology
Background:
- Cholestasis, a condition of impaired bile flow, is associated with altered endogenous opioid system activity.
- Understanding these changes is crucial for elucidating cholestasis pathophysiology.
Purpose of the Study:
- To quantify changes in endogenous opioid activity in rats with acute cholestasis.
- To investigate the specific role of methionine-enkephalin in elevated opioid levels during cholestasis.
Main Methods:
- Acute cholestasis was induced in rats via bile duct resection.
- Total plasma opioid activity was measured using a radioreceptor assay with [3H]-DAMGO.
- Plasma methionine-enkephalin levels were quantified using radioimmunoassay and validated with HPLC.
Main Results:
- Bile duct-resected rats showed a threefold increase in total plasma opioid activity compared to controls.
- Plasma methionine-enkephalin levels were significantly elevated (6-fold vs. sham, 17-fold vs. unoperated).
- Methionine-enkephalin constituted less than 5% of total opioid activity, and was stable in vitro, suggesting reduced degradation.
Conclusions:
- Elevated plasma opioid activity and methionine-enkephalin levels are characteristic of cholestasis in rats.
- Reduced degradation of methionine-enkephalin may contribute to its increased plasma concentration.
- These findings support the hypothesis that endogenous opioids are involved in the pathophysiology of cholestasis.