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

1993; Wiley; Volume: 60; Issue: 2 Linguagem: Inglês

10.1111/j.1471-4159.1993.tb03214.x

1471-4159

Jacob Barg, Mariana M. Belcheva, Robert J. McHale, Rivka Levy, Zvi Vogel, Carmine Coscia,

Neuroendocrine regulation and behavior

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 IC 50 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.