Saransaari P, Oja S S
Tampere Brain Research Center, University of Tampere Medical School, Finland.
Neuroscience. 1999;89(4):1103-11. doi: 10.1016/s0306-4522(98)00417-5.
The effects of the nitric oxide-generating compounds hydroxylamine, sodium nitroprusside and S-nitroso-N-acetylpenicillamine, and the nitric oxide synthase inhibitors nitroarginine and 7-nitroindazole on taurine release from hippocampal slices from adult (three-month-old) and developing (seven-day-old) mice were characterized using a superfusion system. The basal release of [3H]taurine was enhanced when the nitric oxide donors were added at the beginning of superfusion, more markedly in the adult than in the immature hippocampus. The effect of hydroxylamine was clearly concentration-dependent. Hydroxylamine also markedly enhanced the release of endogenous taurine. The K+-stimulated (50 mM) release of taurine was generally inhibited by the nitric oxide-generating compounds in both age groups. Nitric oxide is thus able to act directly at presynaptic terminals, modulating taurine release as a retrograde messenger. The N-methyl-D-aspartate-evoked taurine release was reduced by the nitric oxide donors, particularly by sodium nitroprusside, in the adult hippocampus, while hydroxylamine and S-nitroso-N-acetylpenicillamine markedly potentiated the release in developing mice. In the immature hippocampus the hydroxylamine-enhanced taurine release seems to involve a Ca2+-independent, Na+-dependent and carrier-mediated process while in adult mice only a part of the hydroxylamine-enhanced release is mediated by the same mechanism. The results show that nitric oxide-generating compounds modify the basal, K+- and N-methyl-D-aspartate-evoked releases of taurine in both adult and immature hippocampus. The enhanced N-methyl-D-aspartate receptor-evoked release may be an important mechanism protecting the immature brain against excitotoxicity.
使用灌流系统研究了一氧化氮生成化合物羟胺、硝普钠和S-亚硝基-N-乙酰青霉胺，以及一氧化氮合酶抑制剂硝基精氨酸和7-硝基吲唑对成年（三个月大）和发育中（七天大）小鼠海马切片中牛磺酸释放的影响。在灌流开始时添加一氧化氮供体时，[3H]牛磺酸的基础释放增加，成年海马中的增加比未成熟海马中更明显。羟胺的作用明显呈浓度依赖性。羟胺还显著增强了内源性牛磺酸的释放。在两个年龄组中，一氧化氮生成化合物通常抑制K+刺激（50 mM）的牛磺酸释放。因此，一氧化氮能够直接作用于突触前终末，作为逆行信使调节牛磺酸释放。在成年海马中，一氧化氮供体，特别是硝普钠，减少了N-甲基-D-天冬氨酸诱发的牛磺酸释放，而羟胺和S-亚硝基-N-乙酰青霉胺在发育中小鼠中显著增强了释放。在未成熟海马中，羟胺增强的牛磺酸释放似乎涉及一个不依赖Ca2+、依赖Na+和载体介导的过程，而在成年小鼠中，只有一部分羟胺增强的释放是由相同机制介导的。结果表明，一氧化氮生成化合物改变了成年和未成熟海马中牛磺酸的基础释放、K+和N-甲基-D-天冬氨酸诱发的释放。增强的N-甲基-D-天冬氨酸受体诱发的释放可能是保护未成熟脑免受兴奋性毒性的重要机制。
