Maynard C L, Diedrich D F
Department of Pharmacology, University of Kentucky, Lexington 40536.
Prog Clin Biol Res. 1988;258:235-47.
In the absence of light, phlorizinyl benzylazide is a potent competitive inhibitor of sugar transport (app. Ki about 1.5 uM) and a reversible inhibitor of chloride exchange (app. Ki about 2 uM) in the normal red cell. It causes additional membrane alterations at about 10-fold higher concentrations which lead to a time-, pH-, temperature-, and cell storage time-dependent increase in cell volume in isosmotic phosphate-buffered saline. This drug effect may be related to its interaction with Bands 3 and 4.5 (both become covalently labeled when the azide is light activated) such that cation conductance is increased. Apparently, a channel is created or widened through which salt and water (but not sucrose) can enter causing cell swelling and eventually lysis. The membrane probe is capable of inhibiting deoxygenation-induced sickling of SS and SC cells; under conditions that cause normal cell bursting, sickle cells swell but do not lyse.
在无光条件下，根皮苷苄基叠氮化物是正常红细胞中糖转运的强效竞争性抑制剂（表观 Ki 约为 1.5 μM）和氯交换的可逆抑制剂（表观 Ki 约为 2 μM）。在约高 10 倍的浓度下，它会引起额外的膜改变，这会导致在等渗磷酸盐缓冲盐水中细胞体积随时间、pH、温度和细胞储存时间而增加。这种药物效应可能与其与带 3 和带 4.5 的相互作用有关（当叠氮化物被光激活时，两者都会被共价标记），从而增加阳离子电导。显然，会形成或拓宽一个通道，盐和水（但不是蔗糖）可以通过该通道进入，导致细胞肿胀并最终裂解。该膜探针能够抑制 SS 和 SC 细胞的脱氧诱导镰变；在导致正常细胞破裂的条件下，镰状细胞会肿胀但不会裂解。
