Haupert G T
Renal Unit, Massachusetts General Hospital, Boston 02114.
Hypertension. 1987 Nov;10(5 Pt 2):I61-6. doi: 10.1161/01.hyp.10.5_pt_2.i61.
We characterized the effect of a small, nonpeptidic molecule isolated from bovine hypothalamus on mammalian Na+, K+-adenosine triphosphatase (ATPase). This hypothalamic factor has been shown to inhibit ATPase activity of purified dog kidney enzyme reversibly with high affinity. This report reviews the mechanism of inhibition. Hypothalamic factor inhibits Na+, K+-ATPase only from the extracellular surface. It prevents the phosphorylation from magnesium and inorganic phosphate of the active site aspartate residue of Na+, K+-ATPase and stabilizes the enzyme in an E2 conformation, preventing a sodium-induced shift from E2 to E1. Binding and dissociation reactions of hypothalamic factor in cultured renal tubular epithelial cells show a time frame different from that in isolated membranes and consistent with physiological relevance. A possible mechanism for the physiological regulation of Na+, K+-ATPase, including a cycle of binding and rapid dissociation in intact renal tubular cells, is discussed.
我们对从牛下丘脑分离出的一种小分子非肽类物质对哺乳动物钠钾 - 腺苷三磷酸酶（ATP酶）的作用进行了表征。已证明这种下丘脑因子能以高亲和力可逆地抑制纯化的犬肾酶的ATP酶活性。本报告综述了其抑制机制。下丘脑因子仅从细胞外表面抑制钠钾 - ATP酶。它阻止钠钾 - ATP酶活性位点天冬氨酸残基由镁和无机磷酸进行磷酸化，并使酶稳定在E2构象，防止钠诱导的从E2到E1的转变。下丘脑因子在培养的肾小管上皮细胞中的结合和解离反应显示出与分离膜中不同的时间框架，且与生理相关性一致。本文讨论了钠钾 - ATP酶生理调节的一种可能机制，包括在完整肾小管细胞中的结合和快速解离循环。
