Abstract
Aim:
To characterize the effect of combined pre- and postnatal morphine exposure on N-methyl-D-aspartate receptor (NMDA) receptor signaling in hippocampal neurons of the offspring of morphine-addicted female rats.
Methods:
Cultured hippocampal neurons and synaptosomes were prepared from neonatal and 2- week-old offspring, respectively, of control or morphine-addicted female rats. The increase in the cytosolic Ca2+ concentration ([Ca2+]i) of cultured cells was measured using Fura-2, and glutamate release from synaptosomes was measured enzymatically.
Results:
Both glutamate and NMDA caused a dose-dependent increase in the [Ca2+]i. The nitric oxide (NO) donor, S-nitrosoglutathione (GSNO), but not 3-morpholinosydnonimine, sodium nitroprusside, and S-nitroso-N-acetylpenicillamine, also induced a [Ca2+]i increase. GSNO and glutathione caused a dose-dependent increase in the [Ca2+]i with respective EC50 values of 56 and 414 μmol/L. Both effects were inhibited by Mg2+ or an NMDA receptor antagonist and were unaffected by the presence of a glutamate scavenger. The other glutathione derivatives, oxidized glutathione, S-methylglutathione, S-ethylglutathione, S-propylglutathione, and S-butylglutathione, the dipeptides, Glu-Cys and Cys- Gly, and the antioxidants, dithiothreitol and mercaptoethanol, failed to induce a [Ca2+]i increase. In addition, glutathione caused a dose-dependent increase in glutamate release from synaptosomes. The maximal responses and the EC50 values for the glutamate-, NMDA-, GSNO-, and glutathione-induced [Ca2+]i increases and the glutathione-induced glutamate release were indistinguishable in the neurons of the offspring from control and morphine-addicted female rats.
Conclusion:
GSNO and glutathione act as NMDA receptor agonists and, in contrast to hippocampal brain slice, combined pre- and postnatal morphine exposure does not modulate NMDA receptor signaling in the cultured hippocampal neurons.
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Project supported by grants from the National Science Council, Taiwan, China (NSC93-2311-B033-002 to TYC and NSC93-2320-B016-043 to SHC).
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Chin, Ty., Chueh, Sh. & Tao, Pl. S-Nitrosoglutathione and glutathione act as NMDA receptor agonists in cultured hippocampal neurons. Acta Pharmacol Sin 27, 853–860 (2006). https://doi.org/10.1111/j.1745-7254.2006.00379.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00379.x
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