Multidisiplinary Centre for Cardiovascular Research, University of Leeds, Leeds, UK.
Purinergic Signal. 2012 Jun;8(2):311-6. doi: 10.1007/s11302-011-9289-9. Epub 2012 Jan 6.
Statins have both cholesterol lowering and anti-inflammatory activities, whether mechanisms underlying their activities are independent remains unclear. The ATP-gated P2X(4) receptor is a pro-inflammatory mediator. Here, we investigate the action of fluvastatin and other cholesterol depleting agents on native and recombinant human P2X(4) receptor. Fluvastatin and mβCD suppressed P2X(4)-dependent calcium influx in THP-1 monocytes, without affecting P2Y receptor responses. mβCD or filipin III suppressed the current density of recombinant human P2X(4) receptors. Human P2X(2) was insensitive to cholesterol depletion. Cholesterol depletion had no effect on intrinsic P2X(4) receptor properties as judged by ATP concentration-response relationship, receptor rundown or current decay during agonist occupancy. These data suggest fluvastatin suppresses P2X(4) activity in monocytes through cholesterol depletion and not by modulating intrinsic channel properties.
他汀类药物具有降低胆固醇和抗炎的双重作用，但它们的作用机制是否独立尚不清楚。三磷酸腺苷门控 P2X（4）受体是一种促炎介质。在这里，我们研究了氟伐他汀和其他耗竭胆固醇的药物对天然和重组人 P2X（4）受体的作用。氟伐他汀和 mβCD 抑制了 THP-1 单核细胞中 P2X（4）依赖性钙内流，而不影响 P2Y 受体反应。mβCD 或 filipin III 抑制了重组人 P2X（4）受体的电流密度。人 P2X（2）对胆固醇耗竭不敏感。从 ATP 浓度反应关系、受体衰减或激动剂占据期间的电流衰减判断，胆固醇耗竭对内在 P2X（4）受体特性没有影响。这些数据表明，氟伐他汀通过胆固醇耗竭而非调节内在通道特性来抑制单核细胞中的 P2X（4）活性。
