Inhibitors of renal epithelial phosphate transport in tumor-induced osteomalacia and uremia.

R. Kumar, J. D. Haugen, E. D. Wieben, J. M. Londowski, Q. Cai

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Tumors such as sclerosing hemangiomas are sometimes associated with hypophosphatemia and osteomalacia, both of which disappear on removal of the tumor. We identified a heat labile, 8,000-25,000 dalton, inhibitor of renal epithelial phosphate transport in supernatants of cultured sclerosing hemangioma cells obtained from a patient with oncogenic osteomalacia and hypophosphatemia. The inhibitor does not alter glucose or alanine transport in renal epithelial cells, and has a mechanism of cellular action distinct from that of parathyroid hormone (PTH) in that it inhibits phosphate transport in renal epithelia without increasing concentrations of cyclic 3',5' adenosine monophosphate (cAMP); it's activity is not blocked by a PTH receptor antagonist. Sclerosing hemangioma cells also produce a material that cross-reacts with antisera directed against PTH and tumor tissue sections immunostain with PTH antibodies. We have characterized a cDNA that encodes the PTH immunoreactive material. In its longest open reading frame the cDNA encodes a protein of 381 amino acids that does not resemble PTH in its primary structure. Opossum kidney cells transfected with the cDNA do not produce a product that inhibits phosphate transport. Dialysates from patients with end-stage renal disease also contain a substance(s) that inhibits phosphate and glucose transport in opossum kidney cells. The inhibitor(s) of phosphate uptake in dialysates is a heat labile, approximately 30,000 dalton substance that inhibits phosphate transport by a cAMP-independent mechanism. Determination of the structures and physiology of these phosphate transport inhibitors is likely to yield insights into the control of phosphate homeostasis.

Original languageEnglish (US)
Pages (from-to)296-305
Number of pages10
JournalProceedings of the Association of American Physicians
Volume107
Issue number3
StatePublished - Oct 1995

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Inhibitors of renal epithelial phosphate transport in tumor-induced osteomalacia and uremia.'. Together they form a unique fingerprint.

Cite this