[Effects of morphine on monosodium glutamate neurotoxicity and its mechanism].
The enhancing effects of morphine on monosodium glutamate (MSG) neurotoxicity and its blocking by naloxone were studied through morphological observation, together with detection of concentrations of intracellular free Ca2+ ([Ca2+]i) by Ca2+ indicator Fura-2/AM and lactate dehydrogenase (LDH) efflux in the bathing medium in primary cultures from 14-17 d old mouse fetal cortex. It was found that 10 min pre-incubation of young cortical neurons (7 day in vitro) with morphine 10(-7) or 10(-6) mol.L-1 substantially increased LDH release from 105.7% +/- 19.0% (treated with MSG alone) to 194.5% +/- 17.7% and 214.0% +/- 9.5% respectively after exposure to MSG 0.1 mmol.L-1, but pre-incubation with morphine (10(-7) or 10(-6) mol.L-1) plus naloxone (0.1 mmol.L-1) reversed the LDH release after treatment with the same concentration of MSG. Morphine (10(-7) or 10(-6) mol.L-1) produced little elevation of [Ca2+]i. However, when combined with MSG (0.1 mmol.L-1) morphine elevated the [Ca2+]i level much more than MSG alone. These results suggest that morphine markedly enhances excitotoxic neuron damage, which can be reversed by naloxone. Overloading of intracellular Ca2+ may be a simultaneous pathological mechanism underlying the neuronal damage and death that occur in excitatory toxicity.
Lin
L
L
School of Medicine, Department of Biochemistry, Nanjing University.
Gu
H M
HM
Zhang
W N
WN
Zhao
X N
XN
Zhang
H Y
HY
Tang
G Z
GZ
Li
M Y
MY
Zhang
Z X
ZX
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D004357:Drug Synergism; D005503:Food Additives / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D012970:Sodium Glutamate / Q000633:toxicity*
D005503:Food Additives; D009270:Naloxone; D009020:Morphine; D007770:L-Lactate Dehydrogenase; D002118:Calcium; D012970:Sodium Glutamate