Endogenous nitric oxide inhibits NMDA- and kainate- responses by a negative feedback system in rat hippocampal neurons.
Involvement of endogenous nitric oxide (NO) on glutamate receptor-mediated response was investigated in neuronal cells cultured from embryonic rat hippocampus. L-NG-Nitroarginine (NOARG), a NO synthase inhibitor, augmented NMDA- and kainate-induced increase in intracellular Ca2+ concentration ([Ca2+]i) measured by fura-2 fluorometry. However, quisqualate-induced response was not affected. The potentiating effect of NOARG was blocked by L-arginine, a substrate for NO synthase. NOARG was also effective when added after glutamate-induced response had reached a steady-state. Hemoglobin itself increased the basal level of [Ca2+]i at concentrations higher than 10 mM, and treatment of the cells with 1.0 mM hemoglobin had no effect on NMDA response. 8-Bromo-cyclic GMP was not effective on NMDA response. These results suggest that endogenous NO inhibits NMDA- and kainate-induced increase in [Ca2+]i as a negative feedback system independent of guanylate cyclase activation.
Tanaka
T
T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Saito
H
H
Matsuki
N
N
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D005246:Feedback; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006454:Hemoglobins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D017459:Receptors, Amino Acid / Q000502:physiology
D005971:Glutamates; D006454:Hemoglobins; D017459:Receptors, Amino Acid; D019335:Nitroarginine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; D018698:Glutamic Acid; D016202:N-Methylaspartate; D001120:Arginine; D006152:Cyclic GMP; D007608:Kainic Acid; D002118:Calcium