Anner B M
Department of Pharmacology, The University of Geneva Medical Center, Switzerland.
Clin Exp Hypertens. 1998 Jul-Aug;20(5-6):489-97. doi: 10.3109/10641969809053227.
The membrane Na,K-ATPase is the driving force for sodium reabsorption in the kidney. Accordingly, Na,K-ATPase has been proposed to be a likely target for the action of a putative natriuretic hormone which would modulate sodium excretion by partial inhibition of renal Na,K-ATPase activity. To examine this hypothesis, it is necessary to isolate inhibitors from body fluids and tissues and to characterize their interaction with Na,K-ATPase in comparison to the plant inhibitors ouabain. Two inhibitors extracted from hypothalamus or hypothalamus-hypophysis have been compared to ouabain with regard to the shape of the dose-response curves and species-dependence. Ouabain inhibited renal Na,K-ATPase with dose-response curves spanning 3 to 5 orders of magnitude and marked species-dependence. By contrast, the brain inhibitors blocked the ATPase activity of isolated renal Na,K-ATPase with steep dose-response curves without species-dependence. Thus, the brain inhibitors are clearly distinct from plant ouabain; their chemical structures remain to be established.
细胞膜钠钾ATP酶是肾脏中钠重吸收的驱动力。因此，有人提出钠钾ATP酶可能是一种假定的利钠激素作用的靶点，该激素可通过部分抑制肾脏钠钾ATP酶活性来调节钠排泄。为了验证这一假设，有必要从体液和组织中分离出抑制剂，并与植物抑制剂哇巴因相比，表征它们与钠钾ATP酶的相互作用。从下丘脑或下丘脑 - 垂体中提取的两种抑制剂，在剂量反应曲线形状和物种依赖性方面与哇巴因进行了比较。哇巴因抑制肾脏钠钾ATP酶，其剂量反应曲线跨越3至5个数量级，且具有明显的物种依赖性。相比之下，脑源性抑制剂以陡峭的剂量反应曲线阻断分离的肾脏钠钾ATP酶的ATP酶活性，且无物种依赖性。因此，脑源性抑制剂明显不同于植物哇巴因；它们的化学结构仍有待确定。
