Troehler U, Bonjour J P, Fleisch H
J Lab Clin Med. 1985 Jul;106(1):23-9.
Bisphosphonates have been recognized as useful therapeutic agents in metabolic bone disease. Earlier studies showed a net renal secretion of 1-hydroxy-ethylidene-1,1-bisphosphonate (HEBP). They suggested a renal cellular uptake of this compound. We further studied this concept by investigating the uptake in vitro of 14C-HEBP by rat renal cortex slices. HEBP was accumulated against a concentration gradient, a process that was dependent on time, temperature, and substrate concentration. Unlike that of 3H-p-aminohippurate, the uptake was not affected by change in medium Na+ or glucose and acetate concentration, or by anoxia and various metabolic inhibitors. It was, however, markedly increased by raising the medium calcium and inorganic phosphate concentration. Equilibrium dialysis with renal cortex homogenates suggests that HEBP binds to a cytosolic macromolecule through a process that exhibits saturability and calcium dependency. In conclusion, the results suggest that the bisphosphonate HEBP can penetrate kidney cells by a process that does not appear to be energy dependent, but is markedly influenced by the extracellular calcium-phosphate concentration.
双膦酸盐已被公认为是治疗代谢性骨病的有效药物。早期研究表明，1-羟基亚乙基-1,1-双膦酸盐（HEBP）存在肾脏净分泌。这些研究提示该化合物可被肾细胞摄取。我们通过研究大鼠肾皮质切片对14C-HEBP的体外摄取进一步探讨了这一概念。HEBP可逆浓度梯度蓄积，这一过程依赖于时间、温度和底物浓度。与3H-对氨基马尿酸不同，介质中Na+、葡萄糖和乙酸盐浓度的变化、缺氧及各种代谢抑制剂均不影响其摄取。然而，提高介质中钙和无机磷酸盐浓度可使其摄取显著增加。用肾皮质匀浆进行的平衡透析表明，HEBP通过一个具有饱和性和钙依赖性的过程与胞质大分子结合。总之，结果提示双膦酸盐HEBP可通过一个似乎不依赖能量但受细胞外钙磷浓度显著影响的过程穿透肾细胞。
