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.
N1 - Funding Information:
This study was supported by the National institutes of Health Grants DK28477 and GM31278.
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.
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U2 - 10.1016/S0952-3278(98)90116-8
DO - 10.1016/S0952-3278(98)90116-8
M3 - Article
C2 - 9610844
AN - SCOPUS:0031900288
SN - 0952-3278
VL - 58
SP - 209
EP - 213
JO - Prostaglandins Leukotrienes and Essential Fatty Acids
JF - Prostaglandins Leukotrienes and Essential Fatty Acids
IS - 3
ER -