Bredt D S, Snyder S H
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 1989 Nov;86(22):9030-3. doi: 10.1073/pnas.86.22.9030.
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.
一氧化氮可介导多种神经递质和调质对血管平滑肌及白细胞的影响，它在大脑中由精氨酸通过一种能化学计量地生成瓜氨酸的酶促活性而形成。我们发现，谷氨酸及相关氨基酸，如N-甲基-D-天冬氨酸，能显著刺激小脑切片中精氨酸向瓜氨酸的转化，且化学计量地伴随着环鸟苷酸（cGMP）水平的升高。Nω-单甲基-L-精氨酸以相同效力阻断瓜氨酸和cGMP的增加。精氨酸以相同效力竞争性逆转Nω-单甲基-L-精氨酸的两种效应。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，而能提高一氧化氮水平的超氧化物歧化酶则增加cGMP的生成。这些数据表明，一氧化氮介导了谷氨酸对cGMP生成的刺激作用。
