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

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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
Volume58
Issue number3
DOIs
StatePublished - Mar 1998

Fingerprint

Parathyroid Hormone
Protein Kinase C
Phosphates
Kidney
Opossums
Arachidonic Acid
Proximal Kidney Tubule
Phosphorylation
Amiloride
Phospholipases A
Ouabain
Cyclic AMP-Dependent Protein Kinases
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Sodium
Proteins

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

20-HETE mediates the effect of parathyroid hormone and protein kinase C on renal phosphate transport. / Silverstein, D. M.; Barac-Nieto, M.; Falck, J. R.; Spitzer, A.

In: Prostaglandins Leukotrienes and Essential Fatty Acids, Vol. 58, No. 3, 03.1998, p. 209-213.

Research output: Contribution to journalArticle

@article{438ff1672fa4481cb466ae47b07d9f0f,
title = "20-HETE mediates the effect of parathyroid hormone and protein kinase C on renal phosphate transport",
abstract = "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.",
author = "Silverstein, {D. M.} and M. Barac-Nieto and Falck, {J. R.} and A. Spitzer",
year = "1998",
month = "3",
doi = "10.1016/S0952-3278(98)90116-8",
language = "English (US)",
volume = "58",
pages = "209--213",
journal = "Prostaglandins Leukotrienes and Essential Fatty Acids",
issn = "0952-3278",
publisher = "Churchill Livingstone",
number = "3",

}

TY - JOUR

T1 - 20-HETE mediates the effect of parathyroid hormone and protein kinase C on renal phosphate transport

AU - Silverstein, D. M.

AU - Barac-Nieto, M.

AU - Falck, J. R.

AU - Spitzer, A.

PY - 1998/3

Y1 - 1998/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0031900288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031900288&partnerID=8YFLogxK

U2 - 10.1016/S0952-3278(98)90116-8

DO - 10.1016/S0952-3278(98)90116-8

M3 - Article

C2 - 9610844

AN - SCOPUS:0031900288

VL - 58

SP - 209

EP - 213

JO - Prostaglandins Leukotrienes and Essential Fatty Acids

JF - Prostaglandins Leukotrienes and Essential Fatty Acids

SN - 0952-3278

IS - 3

ER -