NITRIC-OXIDE MEDIATES GLUTAMATE-LINKED ENHANCEMENT OF CGMP LEVELS IN THE CEREBELLUM
NITRIC-OXIDE MEDIATES GLUTAMATE-LINKED ENHANCEMENT OF CGMP LEVELS IN THE CEREBELLUM
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DOI：
10.1073/pnas.86.22.9030
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发表时间：
1989-11-01
影响因子：
11.1
通讯作者：
SNYDER, SH
中科院分区：
文献类型：
--
作者：
BREDT, DS;SNYDER, SH
一氧化氮可介导多种神经递质和调节剂对血管平滑肌和白细胞的作用，它可在大脑中由精氨酸通过一种按化学计量生成瓜氨酸的酶促反应形成。我们发现，谷氨酸及相关氨基酸，如N - 甲基 - D - 天冬氨酸，可显著刺激小脑切片中精氨酸 - 瓜氨酸的转化，同时按化学计量提高环鸟苷酸（cGMP）水平。Nω - 单甲基 - L - 精氨酸能同等效力地阻断瓜氨酸和cGMP的增加。精氨酸能以相同效力竞争性逆转Nω - 单甲基 - L - 精氨酸的这两种作用。能与一氧化氮结合的血红蛋白可阻止N - 甲基 - D - 天冬氨酸对cGMP水平的刺激作用，而能提高一氧化氮水平的超氧化物歧化酶可增加cGMP的生成。这些数据证实一氧化氮介导了谷氨酸对cGMP生成的刺激作用。
Nitric oxide, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes, can be formed in the brain from arginine by an enzymatic activity that stoichiometrically generates citrulline. We show that glutamate and related amino acids, such as N-methyl-D-aspartate, markedly stimulate arginine-citrulline transformation in cerebellar slices stoichiometrically with enhancement of cGMP levels. N.omega.-monomethyl-L-arginine blocks the augmentation both of citrulline and cGMP with identical potencies. Arginine competitively reverses both effects of N.omega.-monomethyl-L-arginine with the same potencies. Hemoglobin, which complexes nitric oxide, prevents the stimulation by N-methyl-D-aspartate of cGMP levels, and superoxide dismutase, which elevates nitric oxide levels, increases cGMP formation. These data establish that nitric oxide mediates the stimulation by glutamate of cGMP formation.