Neyses L, Stimpel M, Locher R, Streuli R, Küffer B, Vetter W
J Hypertens Suppl. 1984 Dec;2(3):S489-92.
The human red blood cell was used as a model system in order to study the effect of cholesterol and its medically important oxidized derivatives (OSC = oxidized sterol compounds) on the calcium entry channel. The calcium-ejecting adenosine triphosphatase (ATPase) was inhibited by vanadate and the influx of 45Ca2-into the cells measured. The cells were loaded with OSC at concentrations between 0.075 and 1.5 micrograms OSC/10(7) cells. Two classes of OSC could be distinguished: one stimulating Ca2+ influx dose-dependently by almost 100% at maximum concentrations, the other inhibiting it dose-dependently by up to 80%. The calcium channel blocker nitrendipine inhibited influx by 70% at 15 microM. More than 90% of the total stimulation or inhibition was accounted for by an influence on the nitrendipine-inhibitable part of influx, i.e. the calcium channel. Cholesterol (incorporated using liposomes) had a stimulatory (+288%), cholesterol depletion an inhibitory effect on calcium influx (-18%). These results demonstrate that cholesterol and its oxidized derivatives modulate the calcium channel in a highly stereospecific manner and provide new insights into the mechanism of action and the atherogenic effect of these compounds.
为了研究胆固醇及其具有重要医学意义的氧化衍生物（OSC = 氧化固醇化合物）对钙进入通道的影响，使用人类红细胞作为模型系统。用钒酸盐抑制钙排出三磷酸腺苷酶（ATPase），并测量45Ca2+进入细胞的内流。细胞以0.075至1.5微克OSC/10(7)细胞的浓度加载OSC。可区分出两类OSC：一类在最大浓度下剂量依赖性地刺激Ca2+内流近100%，另一类剂量依赖性地抑制Ca2+内流高达80%。钙通道阻滞剂尼群地平在15 microM时抑制内流70%。超过90%的总刺激或抑制是由于对尼群地平可抑制的内流部分（即钙通道）的影响。胆固醇（使用脂质体掺入）具有刺激作用（+288%），胆固醇耗竭对钙内流具有抑制作用（-18%）。这些结果表明，胆固醇及其氧化衍生物以高度立体特异性的方式调节钙通道，并为这些化合物的作用机制和致动脉粥样硬化作用提供了新的见解。
