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Abstract We recently demonstrated that δ-opioid receptor (DOR) activation protects cortical neurons against glutamate-induced injury. Because glutamate is a mediator of hypoxic injury in neurons, we hypothesized that DOR is involved in neuroprotection during O 2 deprivation and that its activation/inhibition may alter neuronal susceptibility to hypoxic stress. In this work, we tested the effect of opioid receptor activation and inhibition on cultured cortical neurons in hypoxia (1% O 2 ). Cell injury was assessed by lactate dehydrogenase release, morphology-based quantification, and live/dead staining. Our results show that 1 ) immature neurons ( days 4 and 6 ) were not significantly injured by hypoxia until 72 h of exposure, whereas day 8 neurons were injured after only 24-h hypoxia; 2 ) DOR inhibition (naltrindole) caused neuronal injury in both day 4 and day 8 normoxic cultures and further augmented hypoxic injury in these neurons; 3 ) DOR activation ( d -Ala 2 , d -Leu 5 enkephalin) reduced neuronal injury in day 8 cultures after 24 h of normoxic or hypoxic exposure and attenuated naltrindole-induced injury with prolonged exposure; and 4 ) μ- or κ-opioid receptor inhibition (β-funaltrexamine or nor-binaltorphimine) had little effect on neurons in either normoxic or hypoxic conditions. Collectively, these data suggest that DOR plays a crucial role in neuroprotection in normoxic and hypoxic environments. cortex hypoxia injury protection opioids Footnotes ↵ * J. Zhang and G. T. Gibney contributed equally to this work. Address for reprint requests and other correspondence: Y. Xia, Yale Univ. School of Medicine, Dept. of Pediatrics, 333 Cedar St., LMP 3107, New Haven, CT 06520 (E-mail: ying.xia@yale.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 10.1152/ajpcell.00226.2001 Copyright © 2002 the American Physiological Society
AJP - Cell Physiology – The American Physiological Society
Published: Jun 1, 2002
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