Renal phosphate transport in humoral hypercalcemia of malignancy.
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.
Sartori
L
L
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Insogna
K L
KL
Barrett
P Q
PQ
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000097:blood / Q000652:urine; D004002:Clodronic Acid / Q000494:pharmacology; D006934:Hypercalcemia / Q000209:etiology / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007984:Leydig Cell Tumor / Q000150:complications / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values
D010710:Phosphates; D004002:Clodronic Acid; D000469:Alkaline Phosphatase; D002118:Calcium