The opiate withdrawal-like reaction experienced by patients with cholestatic liver disease after the ingestion of the opiate antagonist nalmefene led to the hypothesis that increased opioidergic neurotransmission/neuromodulation in the central nervous system (CNS) contributes to the pathophysiology of cholestasis. The state of antinociception, which is stereospecifically reversed by naloxone, documented in rats with cholestasis from bile duct resection supports this hypothesis. To further study the opioid system in this animal model of cholestasis, we studied the release of endogenous opioid peptides into the extracellular fluid of the dorso-lateral striatum by the technique of in-vivo microdialysis. Total opioid peptide concentration in the dialysate was measured by a solid phase radioimmunoassay with an antibody directed against the N-terminus of the Tyr-Gly-Gly-Phe-X amino acid sequence after acetylation. Basal total opioid peptide release was significantly higher after surgery in both sham resected and bile duct resected animals. However, basal (unstimulated) total opioid peptide release in the striatum of rats was not altered by cholestasis. It is inferred that the opioidergic abnormalities of cholestasis are not associated with an appreciable increase in the release of endogenous opioids into the extracellular fluid of the striatum. Abnormal processing of specific opioid peptides in cholestasis however, cannot be excluded.
- Bile duct resection
- Endogenous opioids
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)