Sodium nitroprusside modulates NMDA response in the rat supraoptic neurons in vitro.
The modulatory effects of NO on N-methyl-D-aspartate (NMDA)-induced response in neurons of the supraoptic nucleus (SON) were studied by intracellular recording and radioimmunoassay of cyclic nucleotides using the rat brain slice preparation. Depolarization induced by 100 microM NMDA was reduced by application of 1 to 3 mM of the NO-donors, sodium nitroprusside, and isosorbide dinitrate in all 8 neurons and in 6 of 10 neurons, respectively. The scavenger for NO, hemoglobin, and the inhibitor of NO synthase, NG-nitro-L-arginine (LNNA) enhanced the NMDA-induced depolarization in four neurons and two of three neurons, respectively. Intracellular cGMP accumulation induced by NMDA was significantly diminished by LNNA. However, NMDA-induced depolarization was not affected by either the protein kinase inhibitor, N-[2-(methylamino)ethyl]-5- isoquinolinesulfonamide dihydrochloride (H-8), or the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). These results indicate that NO reduces NMDA-induced depolarization in a manner that is independent of cGMP and may control the activity of the SON neurons through NMDA receptors.
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Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Inenaga
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Nagatomo
T
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Yamashita
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H
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D006152:Cyclic GMP / Q000378:metabolism; D005292:Ferricyanides / Q000494:pharmacology; D066298:In Vitro Techniques; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects*
D005292:Ferricyanides; D009599:Nitroprusside; D019335:Nitroarginine; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D001120:Arginine; D011494:Protein Kinases; D006152:Cyclic GMP; D007548:Isosorbide Dinitrate; D007608:Kainic Acid; C028033:potassium ferricyanide