Nagineni C N, Misra B C, Lee D B, Yanagawa N
Transplant Proc. 1987 Feb;19(1 Pt 2):1358-62.
Rabbit PTC concentrated CsA rapidly and reached saturation by two to three minutes. CsA uptake was temperature dependent but was not altered by replacement of uptake medium Na with K or mannitol, changes in extracellular pH, and the presence of metabolic inhibitors or organic anions and cations. The organic Ca channel blockers verapamil and diltiazem and the inorganic Ca channel blocker cadmium caused significant inhibition in both Ca and CsA uptake by PTC. Other Ca transport modulators, ruthenium red and trifluoroperazine, decreased PTC Ca uptake, and A23187 increased PTC Ca uptake, but they were all without effect on CsA uptake. We propose that the CsA uptake pathway through PTC is situated at or close to Ca channels so that changes induced by Ca channel blockers also affect transit of CsA through the CsA "passageway." The close spatial relationship between CsA and Ca channels also raises the possibility that CsA uptake may intiate Ca channel-related activities, thereby leading to a cascade of Ca-dependent processes and causing nephrotoxicity. A hypothesis is depicted in Fig 1.
兔近端小管细胞（PTC）能迅速浓缩环孢素A（CsA），并在两到三分钟内达到饱和。CsA的摄取依赖于温度，但用钾或甘露醇替代摄取培养基中的钠、细胞外pH值的变化以及代谢抑制剂或有机阴离子和阳离子的存在均不会改变其摄取。有机钙通道阻滞剂维拉帕米和地尔硫䓬以及无机钙通道阻滞剂镉可显著抑制PTC对钙和CsA的摄取。其他钙转运调节剂钌红和三氟拉嗪可降低PTC对钙的摄取，而A23187可增加PTC对钙的摄取，但它们对CsA的摄取均无影响。我们认为，PTC摄取CsA的途径位于钙通道处或其附近，因此钙通道阻滞剂引起的变化也会影响CsA通过“通道”的转运。CsA与钙通道之间紧密的空间关系也增加了一种可能性，即CsA的摄取可能引发与钙通道相关的活动，从而导致一系列钙依赖性过程并引起肾毒性。图1展示了一个假设。
