20-HETE mediates the effect of parathyroid hormone and protein kinase C on renal phosphate transport

D. M. Silverstein, M. Barac-Nieto, J. R. Falck, A. Spitzer

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17 Scopus citations


Parathyroid hormone (PTH) is a major inhibitor of renal proximal tubule (PT) sodium-dependent phosphate (Na+-Pi) cotransport. PTH is thought to exert its effect on Pi transport in the PT via the protein kinase A (PKA) and C (PKC) intracellular signalling pathways. PKC-dependent phosphorylation of phospholipase A, stimulates arachidonic acid (AA) release, the latter a potent inhibitor of Pi transport. In turn, AA is metabolized to 20-hydroxyeicosatetraenoic acid (20-HETE) in the PT. In addition, 20-HETE production is stimulated by PTH. We therefore explored the possibility that 20-HETE may mediate the PTH/PKC inhibition of renal Na+-Pi cotransport. To this end, we tested the effect of 20-HETE on Na+-Pi cotransport in proximal tubule-like cells. Exposure of opossum kidney (OK) cells for 4 h to 20-HETE (10-7 M) decreased Na+-dependent uptake of 32pi (from 0.26 ± 0.02 to 0.19 ± 0.01 nmol/mg protein.min) by ~25% (P< 0.001). The inhibition was due to a reduction in V(max). 20-HETE had no significant effect on either the apical amiloride-sensitive and insensitive 22Na uptakes or on basolateral ouabain-sensitive 86Rb uptake, and was specific for Pi. These results indicate that 20-HETE specifically inhibits Na+-dependent Pi transport in OK cells and that it may be a mediator of PTH action in the PT.

Original languageEnglish (US)
Pages (from-to)209-213
Number of pages5
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Issue number3
StatePublished - Mar 1998

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology


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