β-Endorphin Is a Potent Inhibitor of Thymidine Incorporation into DNA via μ and κ-Opioid Receptors in Fetal Rat Brain Cell Aggregates in Culture

Abstract: Thymidine incorporation into DNA was inhibited dose-dependently by β-endorphin in rat fetal brain cell aggregate cultures. The inhibition was reversed partially by μ (cyclic D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide) or k (norbinaltorphimine) antagonists. Complete blockade of the β-endorphin inhibitory effect was achieved only on concomitant exposure to both antagonists. Eadie–Hofstee analysis revealed that β-endorphin inhibited thymidine incorporation noncompetitively. In the presence of protease inhibitors, β-endorphin decreased thymidine incorporation with an IC₅₀ of 0.7 n M . Truncated and N -acetylated β-endorphin derivatives, which bind with low affinity to opioid receptors, did not affect thymidine incorporation. These findings indicate that β-endorphin at physiological concentrations can regulate thymidine incorporation in cultured brain cells.