Beta-endorphin is a potent inhibitor of thymidine incorporation into DNA via mu- and kappa-opioid receptors in fetal rat brain cell aggregates in culture.
Thymidine incorporation into DNA was inhibited dose-dependently by beta-endorphin in rat fetal brain cell aggregate cultures. The inhibition was reversed partially by mu (cyclic D-Phe-Cys-Tyr-D-Trp-Orn-Thr- Pen-Thr amide) or kappa (norbinaltorphimine) antagonists. Complete blockade of the beta-endorphin inhibitory effect was achieved only on concomitant exposure to both antagonists. Eadie-Hofstee analysis revealed that beta-endorphin inhibited thymidine incorporation noncompetitively. In the presence of protease inhibitors, beta-endorphin decreased thymidine incorporation with an IC50 of 0.7 nM. Truncated and N-acetylated beta-endorphin derivatives, which bind with low affinity to opioid receptors, did not affect thymidine incorporation. These findings indicate that beta-endorphin at physiological concentrations can regulate thymidine incorporation in cultured brain cells.
E. A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, MO 63104-1079.
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Belcheva
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Levy
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Coscia
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002449:Cell Aggregation; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D020881:Enkephalin, D-Penicillamine (2,5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D005333:Fetus; D007700:Kinetics; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism*; D014316:Tritium; D001615:beta-Endorphin / Q000031:analogs & derivatives / Q000494:pharmacology*
D004745:Enkephalins; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014316:Tritium; D001615:beta-Endorphin; D016308:Enkephalin, Leucine-2-Alanine; D020881:Enkephalin, D-Penicillamine (2,5)-; D004247:DNA; D013936:Thymidine