Mihic S J, Wu P H, Kalant H
Department of Pharmacology, Faculty of Medicine, University of Toronto, Ont., Canada.
Can J Physiol Pharmacol. 1988 Aug;66(8):1035-40. doi: 10.1139/y88-169.
The reported effects of norepinephrine (NE) on brain Na+-K+ ATPase are quite variable. Different investigators have reported activation, inhibition, or no effect. An investigation of the importance of reaction conditions on brain Na+-K+ ATPase activity was undertaken to resolve some of these discrepancies. Using porcine cerebral cortical Na+-K+ ATPase and rat brain synaptosomal membrane preparations, it was observed that NE strongly inhibited brain Na+-K+ ATPase in Tris-HCl buffer. This inhibition of the enzyme was reversed by the addition of EDTA. In contrast, NE did not significantly inhibit Na+-K+ ATPase in imidazole-glycylglycine and Krebs-Ringer-phosphate buffers. This buffer dependence of NE inhibition of the enzyme was consistently demonstrated with three different established methods for phosphate measurement. Kinetic analysis indicated that NE, in Tris-HCl buffer, inhibited the enzyme noncompetitively at high affinity, and competitively at low affinity, ATP substrate sites.
去甲肾上腺素（NE）对脑钠钾ATP酶的影响报道不一。不同研究者分别报道了其激活、抑制或无作用的情况。为了解决其中一些差异，对反应条件对脑钠钾ATP酶活性的重要性进行了研究。使用猪脑皮质钠钾ATP酶和大鼠脑突触体膜制剂，观察到在Tris-HCl缓冲液中NE强烈抑制脑钠钾ATP酶。加入EDTA可逆转该酶的这种抑制作用。相比之下，在咪唑-甘氨酰甘氨酸和磷酸 Krebs-Ringer缓冲液中，NE对钠钾ATP酶无明显抑制作用。用三种不同的既定磷酸盐测量方法一致证明了NE对该酶的抑制作用存在缓冲液依赖性。动力学分析表明，在Tris-HCl缓冲液中，NE在高亲和力ATP底物位点以非竞争性方式抑制该酶，在低亲和力ATP底物位点以竞争性方式抑制该酶。
