Sartori L, Insogna K L, Barrett P Q
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Am J Physiol. 1988 Dec;255(6 Pt 2):F1078-84. doi: 10.1152/ajprenal.1988.255.6.F1078.
Fisher rats bearing the H-500 Leydig cell tumor (LCT) develop humoral hypercalcemia of malignancy (HHM), which is accompanied by hypophosphatemia and hyperphosphaturia. To better define the mechanisms underlying the changes in phosphate metabolism, the activity of sodium-dependent phosphate uptake (Na+-Pi) in microvillus membrane vesicles (MMV) isolated from the renal cortex of LCT-bearing rats was studied. Ten days after tumor transplantation the animals became hypercalcemic, hypophosphatemic, and hyperphosphaturic, and LCT-MMV showed a specific decrease in Na+-Pi. A kinetic analysis revealed evidence for both a high- and a low-affinity system of Na+-Pi. The Vmax of both the low-affinity system and the high-affinity system were significantly reduced in LCT-MMV. These changes in Na+-Pi transport were similar to those induced by parathyroid hormone. In day-10 tumor-bearing animals, daily injections of dichloromethylene diphosphonate (2.5 mg.kg-1.day-1) prevented the onset of hypercalcemia but not the reduction in Na+-Pi in LCT-MMV. Our data suggest that in this animal model of HHM there is a specific and persistent impairment of Na+-Pi uptake at the level of the renal cortical brush-border membrane, which contributes to the derangement in phosphate metabolism.
携带H - 500间质细胞瘤（LCT）的Fisher大鼠会发生恶性肿瘤体液性高钙血症（HHM），伴有低磷血症和高磷尿症。为了更好地确定磷代谢变化的潜在机制，研究了从携带LCT大鼠肾皮质分离的微绒毛膜囊泡（MMV）中钠依赖性磷摄取（Na⁺-Pi）的活性。肿瘤移植10天后，动物出现高钙血症、低磷血症和高磷尿症，且LCT - MMV的Na⁺-Pi出现特异性降低。动力学分析揭示了Na⁺-Pi存在高亲和力和低亲和力系统的证据。LCT - MMV中低亲和力系统和高亲和力系统的Vmax均显著降低。Na⁺-Pi转运的这些变化与甲状旁腺激素诱导的变化相似。在移植肿瘤10天的动物中，每日注射二氯亚甲基二膦酸盐（2.5 mg·kg⁻¹·天⁻¹）可预防高钙血症的发生，但不能阻止LCT - MMV中Na⁺-Pi的降低。我们的数据表明，在这个HHM动物模型中，肾皮质刷状缘膜水平的Na⁺-Pi摄取存在特异性和持续性损伤，这导致了磷代谢紊乱。
