Morphine prevents peroxynitrite-induced death of human neuroblastoma SH-SY5Y cells through a direct scavenging action

N-Ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine (NOC12), a nitr ic oxide donor, 3-morpholinosydnonimine (SIN-1), a generator of peroxynitri te (ONOO-), and peroxynitrite induced cell death accompanied by DNA fragmen tation in human neuroblastoma SH-SY5Y cell cultures. Morphine prevented the cell death induced by SIN-1 or peroxynitrite, but not that induced by NOC1 2. The protective effect of morphine was concentration-dependent (10-100 mu M), but was not antagonized by naloxone. The selective ligands for opioid receptor subtypes, [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]enkephalin (DAMGO, mu- opioid receptor agonist), [D-Pen(2,5)]enkephalin (DPDPE, delta-opioid recep tor agonist) and trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cy clohexyl)benzeneacetamide (U-50488, kappa-opioid receptor agonist) even at the concentration of 100 mu M did not prevent the cell death induced by SIN -1. From measurement of the absorbance spectrum of peroxynitrite, the decom position of peroxynitrite in 0.25 M potassium phosphate buffer (pH 7.4) was Very rapid and complete within seconds. However, the absorbance was very s table in the presence of morphine. In addition, morphine inhibited peroxyni trite-induced nitration of tyrosine in a concentration-dependent manner. Th ese results indicate that morphine rapidly reacts with peroxynitrite. The p resent study showed that morphine prevented peroxynitrite-induced cell deat h through its direct scavenging action, suggesting that morphine can protec t cells against damage caused by peroxynitrite. (C) 1999 Elsevier Science B .V. All rights reserved.