3-叠氮乙酰毒毛花苷元（毒毛花苷元的一种光化学类似物）对钠钾ATP酶的强心部位定向不可逆抑制作用

Cardiotonic site directed irreversible inhibition of Na+ + K+-ATPase by 3-azidoacetylstrophanthidin, a photochemical analogue of strophanthidin.

作者信息

Tobin T, Akera T, Brody T M, Taneja H R

出版信息

Eur J Pharmacol. 1976 Jan;35(1):69-76. doi: 10.1016/0014-2999(76)90301-0.

Abstract

A photochemical analogue of strophanthidin, 3-azidoacetylstrophanthidin (AAS) was synthesized and tested as a cardiotonic steroid (CS) site directed photoaffinity label for Na+ + K+-ATPase (ATP phosphohydrolase, E.C. 3.6.1.3). AAS-inhibited rat brain ATPase with an I50 of about 1 x 10(-6) M readily displaced 3H-ouabain from its specific binding sites on this enzyme and produced a positive inotropic effect in guinea pig atrial strips. In the absence of UV light its interaction with the CS binding sites of Na+ + K+-ATPase appeared reversible. In the presence of UV light and acetylphosphate, AAS produced about 15% irreversible inhibition of Na+ + K+-ATPase, compared with about 5% irreversible inhibition in the absence of either UV light or acetyl phosphate. Since acetylphosphate supports specific glucoside binding at the CS binding sites of Na+ + K+-ATPase these data are consistent with the concept that AAS is a cardiotonic steroid site directed photoactivatable inhibitor of Na+ + K+-ATPase.

摘要

合成了毒毛花苷元的光化学类似物3-叠氮乙酰毒毛花苷元（AAS），并将其作为强心甾体（CS）位点导向的光亲和标记物用于Na⁺+K⁺-ATP酶（ATP磷酸水解酶，E.C. 3.6.1.3）进行测试。AAS对大鼠脑ATP酶的抑制作用的半数抑制浓度（I50）约为1×10⁻⁶M，它能轻易地将³H-哇巴因从该酶的特异性结合位点上置换下来，并在豚鼠心房肌条上产生正性肌力作用。在无紫外光的情况下，它与Na⁺+K⁺-ATP酶的CS结合位点的相互作用似乎是可逆的。在有紫外光和乙酰磷酸存在的情况下，与在无紫外光或乙酰磷酸时约5%的不可逆抑制相比，AAS对Na⁺+K⁺-ATP酶产生了约15%的不可逆抑制。由于乙酰磷酸支持在Na⁺+K⁺-ATP酶的CS结合位点上特异性糖苷的结合，这些数据与AAS是Na⁺+K⁺-ATP酶的强心甾体位点导向的可光活化抑制剂这一概念是一致的。