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一氧化氮生成药物对猪大脑皮层纯化的(钠,钾)-ATP酶活性的抑制作用。

Inhibition of purified (Na+,K+)-ATPase activity from porcine cerebral cortex by NO generating drugs.

作者信息

Sato T, Kamata Y, Irifune M, Nishikawa T

机构信息

Department of Pharmacology, Kagoshima University Dental School, Japan.

出版信息

Brain Res. 1995 Dec 15;704(1):117-20. doi: 10.1016/0006-8993(95)01165-x.

DOI:10.1016/0006-8993(95)01165-x
PMID:8750971
Abstract

We tested the effects of several nitric oxide (NO) generating compounds on the activity of sodium-potassium adenosine 5'-triphosphatase [(Na+,K+)-ATPase] purified from porcine cerebral cortex. Sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine (SIN-1) and (d1)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (NOR 3) inhibited the (Na+,K+)-ATPase activity dose dependently. Superoxide dismutase, a NO scavenger, and sulfhydryl (SH) compounds, reduced-form glutathione (rGSH) and dithiothreitol (DTT), prevented the inhibitory action of SNAP, SIN-1 and NOR 3 but not of SNP, when applied simultaneously with NO generating compounds, and this enzyme inhibition could be reactivated by the incubation with these SH compounds but not with SOD. The inhibitory action by SNP was magnified by simultaneous application of DTT. These results suggest that NO generating compounds, SNAP, SIN-1 and NOR 3 but not SNP, may release NO or NO-derived products and may inhibit (Na+,K+)-ATPase activity by interacting with a SH group at the active site of the enzyme.

摘要

我们测试了几种一氧化氮(NO)生成化合物对从猪脑皮层纯化的钠钾腺苷三磷酸酶[(Na +,K +)-ATP酶]活性的影响。硝普钠(SNP)、S-亚硝基-N-乙酰青霉胺(SNAP)、3-吗啉代辛二亚胺(SIN-1)和(d1)-(E)-乙基-2-[(E)-羟基亚氨基]-5-硝基-3-己烯酰胺(NOR 3)均剂量依赖性地抑制(Na +,K +)-ATP酶活性。超氧化物歧化酶(一种NO清除剂)以及巯基(SH)化合物(还原型谷胱甘肽(rGSH)和二硫苏糖醇(DTT))在与NO生成化合物同时应用时,可阻止SNAP、SIN-1和NOR 3的抑制作用,但不能阻止SNP的抑制作用,并且这种酶抑制作用可通过与这些SH化合物孵育而重新激活,但不能通过与超氧化物歧化酶孵育重新激活。同时应用DTT可增强SNP的抑制作用。这些结果表明,NO生成化合物SNAP、SIN-1和NOR 3而非SNP可能释放NO或NO衍生产物,并可能通过与酶活性位点的SH基团相互作用来抑制(Na +,K +)-ATP酶活性。

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