Opioids disrupt Ca2+ homeostasis and induce carbonyl oxyradical production in mouse astrocytes in vitro: transient increases and adaptation to sustained exposure.
Pharmacologically distinct subpopulations of astroglia express mu, delta, and/or kappa opioid receptors. Activation of mu, delta, or kappa 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+]i and carbonyl oxidation products within individual murine astrocytes. Acute (3 h) exposure to mu; (H-Tyr-Pro-Phe (N-Me) -D-Pro-NH2; PLO17), delta ([D-Pen2, D-Pen5]-enkephalin), and kappa (trans-(+/-)-3, 4-dichloro-N-methyl-N-[2-(1-pyrr olidinyl) cyclohexyl] benzeneacetamide methanesulfonate; U50,488H) opioid agonists caused significant mean increases in [Ca2+]i and in the levels of oxidative products in astrocytes. In contrast, following 72 h of continuous opioid exposure, [Ca2+]i and carbonyl levels returned to normal, irrespective of opioid treatment. These preliminary findings indicate that opioids initially destabilize [Ca2+]i and increase reactive oxygen species in astrocytes; however, astrocytes later recover and adapt to sustained opioid exposure.
Hauser
K F
KF
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0084, USA.
Harris-White
M E
ME
Jackson
J A
JA
Opanashuk
L A
LA
Carney
J M
JM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004361:Drug Tolerance; D004723:Endorphins / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors
D000700:Analgesics; D018712:Analgesics, Non-Narcotic; D004723:Endorphins; D004745:Enkephalins; D009292:Narcotic Antagonists; D009294:Narcotics; D017382:Reactive Oxygen Species; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C044708:morphiceptin, N-Me-Phe(3)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D002118:Calcium