Nitric oxide synthase inhibitor decrease NMDA-induced elevations of extracellular glutamate and intracellular ca(2+) levels via a cGMP-independent mechanism in cerebellar granule neurons

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Title
Nitric oxide synthase inhibitor decrease NMDA-induced elevations of extracellular glutamate and intracellular ca(2+) levels via a cGMP-independent mechanism in cerebellar granule neurons
Author(s)
Sei Kwan Oh; Bong Sik Yun; In Ja Ryoo; Patrick P McCaslin; Ick Dong Yoo
Bibliographic Citation
Archives of Pharmacal Research, vol. 22, no. 1, pp. 48-54
Publication Year
1999
Abstract
These studies were designed to examine the differential effect of nitric oxide (NO) and cGMP on glutamate neurotransmission. In primary cultures of rat cerebellar granule cells, the glutamate receptor agonist N-methyl-D-aspartate (NMDA) stimulates the elevation of intracellular calcium concentration ([Ca2+]i), the release of glutamate, the synthesis of NO and an increase of cGMP. Although NO has been shown to stimulate guanylyl cyclase, it is unclear yet whether NO alters the NMDA-induced glutamate release and [Ca2+]i elevation. We showed that the NO synthase inhibitor, NG-monomethyl-L-arginine (NMMA), partially prevented the NMDA-induced release of glutamate and elevation of [Ca2+]i and completely blocked the elevation of cGMP. These effects of NO on glutamate release and [Ca2+]i elevation were unlikely to be secondary to cGMP as the cGMP analogue, dibutyryl cGMP (dBcGMP), did not suppress the effects of NMDA. Rather, dBcGMP slightly augmented the NMDA-induced elevation of [Ca2+]i with no change in the basal level of glutamate or [Ca2+]i. The extracellular NO scavenger hydroxocobalamine prevented the NMDA-induced release of glutamate providing indirect evidence that the effect of NO may act on the NMDA receptor. These results suggest that low concentration of NO has a role in maintaining the NMDA receptor activation in a cGMP-independent manner.
Keyword
NMDANG-Monomethyl-L-arginineDibutyryl-cGMPCa2+ influxHydroxocobalaminGlutamate release
ISSN
0253-6269
Publisher
Pharmaceutical Soc Korea
DOI
http://dx.doi.org/10.1007/BF02976435
Type
Article
Appears in Collections:
Ochang Branch Institute > Anticancer Agent Research Center > 1. Journal Articles
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