OPIOIDS DISRUPT CA2-VITRO - TRANSIENT INCREASES AND ADAPTATION TO SUSTAINED EXPOSURE( HOMEOSTASIS AND INDUCE CARBONYL OXYRADICAL PRODUCTIONIN MOUSE ASTROCYTES IN)

Pharmacologically distinct subpopulations of astroglia express mu, del ta, and/or kappa opioid receptors. Activation of mu, delta, or kappa o pioid receptors can destabilize intracellular calcium ([Ca2+](i)) in a strocytes leading to cellular hypertrophy and reactive injury. To asse ss whether acute or sustained opioid exposure might adversely affect a stroglial function by disrupting Ca2+ homeostasis or by producing reac tive oxygen species, fura-2 and a novel fluorescent-tagged biotin-4-am idobenzoic hydrazide reagent, respectively, were used to detect [Ca2+] (i) and carbonyl oxidation products within individual murine astrocyte s. Acute (3 h) exposure to mu (H-Tyr-Pro-Phe (N-Me)-D-Pro-NH2; PLO17), delta ([D-Pen(2),D-Pen(5)]-enkephalin), and kappa -(+/-)-3,4-dichloro -N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeneacetamide methanesu lfonate; U50,488H) opioid agonists caused significant mean increases i n [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. (C) 1998 Academic Press.