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

Rajiv Kumar, J. D. Haugen, Eric D Wieben, J. M. Londowski, Q. Cai

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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

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Uremia
Phosphates
Kidney
Parathyroid Hormone
Benign Fibrous Histiocytoma
Hypophosphatemia
Opossums
Complementary DNA
Dialysis Solutions
Cyclic AMP
Hot Temperature
Parathyroid Hormone Receptor Type 1
Glucose
Neoplasms
Osteomalacia
Oncogenic osteomalacia
Alanine
Open Reading Frames
Chronic Kidney Failure
Immune Sera

ASJC Scopus subject areas

  • Medicine(all)

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Inhibitors of renal epithelial phosphate transport in tumor-induced osteomalacia and uremia. / Kumar, Rajiv; Haugen, J. D.; Wieben, Eric D; Londowski, J. M.; Cai, Q.

In: Proceedings of the Association of American Physicians, Vol. 107, No. 3, 10.1995, p. 296-305.

Research output: Contribution to journalArticle

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