Opioids Disrupt Ca2+Homeostasis and Induce Carbonyl Oxyradical Production in Mouse Astrocytesin Vitro:Transient Increases and Adaptation to Sustained Exposure

doi:10.1006/exnr.1998.6788

Experimental Neurology

Volume 151, Issue 1, May 1998, Pages 70-76

https://doi.org/10.1006/exnr.1998.6788 Get rights and content

Abstract

Pharmacologically distinct subpopulations of astroglia express μ, δ, and/or κ opioid receptors. Activation of μ, δ, or κ opioid receptors can destabilize intracellular calcium ([Ca²⁺]_i) in astrocytes leading to cellular hypertrophy and reactive injury. To assess whether acute or sustained opioid exposure might adversely affect astroglial function by disrupting Ca²⁺homeostasis or by producing reactive oxygen species, fura-2 and a novel fluorescent-tagged biotin-4-amidobenzoic hydrazide reagent, respectively, were used to detect [Ca²⁺]_iand carbonyl oxidation products within individual murine astrocytes. Acute (3 h) exposure to μ (H-Tyr-Pro-Phe (N-Me) -D-Pro-NH₂; PLO17), δ ([D-Pen², D-Pen⁵]-enkephalin), and κ (trans-(±)-3,4-dichloro-N-methyl-N-[2-(1-pyrr olidinyl) cyclohexyl] benzeneacetamide methanesulfonate; U50,488H) opioid agonists caused significant mean increases in [Ca²⁺]_iand in the levels of oxidative products in astrocytes. In contrast, following 72 h of continuous opioid exposure, [Ca²⁺]_iand carbonyl levels returned to normal, irrespective of opioid treatment. These preliminary findings indicate that opioids initially destabilize [Ca²⁺]_iand increase reactive oxygen species in astrocytes; however, astrocytes later recover and adapt to sustained opioid exposure.

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^☆: H. KettenmannB. R. Ransom

¹: Present address: Department of Medicine, UCLA/SFVP, 16111 Plummer Street (MC151), Sepulveda, CA 91343. E-mail: [email protected].

²: Present address: Centaur Pharmaceuticals, Inc., 484 Oakmead Parkway, Sunnyvale, CA 94086.

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Regular ArticleOpioids Disrupt Ca2+Homeostasis and Induce Carbonyl Oxyradical Production in Mouse Astrocytesin Vitro:Transient Increases and Adaptation to Sustained Exposure☆

Abstract

Eur. J. Pharmacol.

Neuroscience

Forensic Sci. Int.

J. Biol. Chem.

Brain Res.

Dev. Brain Res.

Neuropeptides

Neuropharmacol.

Exp. Neurol.

Exp. Neurol.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Methods Cell Biol.

Trends Neurosci.

Neuron

Mol. Brain Res.

Neuroscience

Dev. Brain Res.

Eur. J. Pharmacol. Mol. Pharmacol.

FEBS Lett.

Drug Alcohol Depend.

Phosphorylation and agonist-specific intracellular trafficking of an epitope-tagged μ-opioid receptor expressed in HEK 293 cells

J. Neurochem.

Glial fibrillary acidic protein and the mesolimbic dopamine system: Regulation by chronic morphine and Lewis–Fischer strain differences in the rat ventral tegmental area

J. Neurochem.

Regular Article
Opioids Disrupt Ca²⁺Homeostasis and Induce Carbonyl Oxyradical Production in Mouse Astrocytesin Vitro:Transient Increases and Adaptation to Sustained Exposure☆