enkephalin--ala(2)-mephe(4)-gly(5)- and Liver-Failure

enkephalin--ala(2)-mephe(4)-gly(5)- has been researched along with Liver-Failure* in 1 studies

Other Studies

1 other study(ies) available for enkephalin--ala(2)-mephe(4)-gly(5)- and Liver-Failure

ArticleYear
Up-regulation of central mu-opioid receptors in a model of hepatic encephalopathy: a potential mechanism for increased sensitivity to morphine in liver failure.
    Life sciences, 2002, Feb-22, Volume: 70, Issue:14

    Increased GABA-mediated neurotransmission, reported to occur in hepatic encephalopathy (HE), is associated with a decrease in the release of Met-enkephalin and the expression of its coding gene in the brain. Furthermore, patients with cirrhosis and a history of HE exhibit increased sensitivity to the neuroinhibitory effects of morphine. Thus, there is a rationale to study the status of the endogenous opioid system in HE. The aim of this study was to determine whether mu-opioid receptors in the brain are up-regulated in a well characterized model of HE. Binding parameters of mu-opioid receptors were derived by assaying the binding of the opiate agonist [3H]-tyr-D-Ala-Gly-N-Methyl-Phe-Gly-ol (DAMGO) to brain membranes from rats with precisely defined stages of HE and control animals. The mean density of mu-opioid receptor sites (Bmax) in rats with stage II, III, and IV HE was 15, 29, and 33% higher, respectively, than the corresponding control value (p<0.01). In addition, the affinity of mu opioid receptors for the agonist (1/Kd) also increased with progression of HE (mean for stage IV HE vs. corresponding control mean, p<0.01). In conclusion, in liver failure, increased density and affinity of central mu-opioid receptors in the brain may: (i) be the basis for the documented increased sensitivity to opiate agonists; and (ii) occur as a consequence of increased GABAergic tone reducing neuronal synthesis and release of opioid agonist peptides.

    Topics: Animals; Brain; Cell Membrane; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; gamma-Aminobutyric Acid; Hepatic Encephalopathy; Liver Failure; Male; Morphine; Rats; Receptors, Opioid, mu; Thioacetamide; Tritium; Up-Regulation

2002