Li X H, Jope R S
Department of Pharmacology, University of Alabama, Birmingham 35294.
Biochem Pharmacol. 1989 Sep 1;38(17):2781-7. doi: 10.1016/0006-2952(89)90431-0.
Sulfur-containing amino acids were found to inhibit norepinephrine-stimulated [3H]phosphoinositide hydrolysis in rat cortical slices. Of the amino acids tested, L-cysteine was the most potent, inhibiting the response by 42 and 85% at concentrations of 50 and 500 microM respectively. L-Cystine and L-serine-O-sulfate also inhibited the response to norepinephrine, but to a lesser degree than did L-cysteine. L-Homocysteic acid slightly potentiated phosphoinositide hydrolysis at a concentration of 100 microM, but caused inhibition at 500 microM. L-Cysteine sulfinate produced effects intermediate to those of L-cysteine and L-homocysteic acid, having no effect on the response to norepinephrine at 50 microM, but causing 84% inhibition at 500 microM. The D-isomers of cysteine and homocysteic acid were much less potent than were the L-isomers. Examination of the time course of the inhibition of norepinephrine-stimulated [3H]phosphoinositide hydrolysis by L-cysteine showed that it was inhibited almost completely after 15, 30, 45 and 60 min of incubation. L-Cysteine and L-homocysteic acid caused similarly strong inhibitions of the production of [3H]inositol monophosphate, [3H]inositol bisphosphate and [3H]inositol trisphosphate. The hydrolysis of [3H]phosphoinositides stimulated by norepinephrine in slices from rat hippocampus and striatum were inhibited by L-cysteine to an extent similar to that occurring in cortical slices. These results demonstrate that several sulfur-containing amino acids, some of which have been proposed to be endogenous excitatory amino acid neurotransmitters, effectively modulate the response to norepinephrine of the phosphoinositide second messenger system in rat brain.
研究发现，含硫氨基酸可抑制去甲肾上腺素刺激大鼠皮层切片中[3H]磷酸肌醇的水解。在所测试的氨基酸中，L-半胱氨酸的作用最强，在浓度分别为50和500微摩尔时，对该反应的抑制率分别为42%和85%。L-胱氨酸和L-丝氨酸-O-硫酸盐也可抑制对去甲肾上腺素的反应，但程度低于L-半胱氨酸。L-高半胱氨酸在浓度为100微摩尔时可轻微增强磷酸肌醇水解，但在500微摩尔时则产生抑制作用。L-半胱氨酸亚磺酸盐的作用介于L-半胱氨酸和L-高半胱氨酸之间，在50微摩尔时对去甲肾上腺素反应无影响，但在500微摩尔时可导致84%的抑制率。半胱氨酸和高半胱氨酸的D-异构体的作用远不如L-异构体。对L-半胱氨酸抑制去甲肾上腺素刺激的[3H]磷酸肌醇水解的时间进程进行检测发现，孵育15、30、45和60分钟后，该反应几乎完全受到抑制。L-半胱氨酸和L-高半胱氨酸对[3H]肌醇单磷酸、[3H]肌醇二磷酸和[3H]肌醇三磷酸的生成产生类似的强烈抑制作用。L-半胱氨酸对去甲肾上腺素刺激大鼠海马体和纹状体切片中[3H]磷酸肌醇水解的抑制程度与在皮层切片中相似。这些结果表明，几种含硫氨基酸可有效调节大鼠脑中磷酸肌醇第二信使系统对去甲肾上腺素的反应，其中一些含硫氨基酸被认为是内源性兴奋性氨基酸神经递质。
