PMID- 2173422
OWN - NLM
STAT- MEDLINE
DCOM- 19901213
LR  - 20171213
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 259
IP  - 5 Pt 2
DP  - 1990 Nov
TI  - 12-HETE modulates Na-coupled uptakes in proximal tubular cells: role of 
      diacylglycerol kinase inhibition.
PG  - F816-22
AB  - Inhibition of diacylglycerol (DAG) kinase, an alternative way to increase the 
      cellular DAG level, was shown to reproduce, in renal proximal tubular cells, the 
      inhibitory effect of protein kinase C (PKC) activators on Na-Pi and 
      Na-alpha-methyl-D-glucopyranoside (MGP) cotransport. To evaluate whether 
      12S-hydroxyeicosatetraenoic acid (12S-HETE) or 12R-HETE, a DAG kinase inhibitor 
      in endothelial cells, has a similar effect in proximal tubular cells, we studied 
      the influence of this lipoxygenase product on Na-dependent uptake of Pi, MGP, and 
      alanine, as well as on [14C]arachidonate-DAG content and [32P]phosphatidic acid 
      (PA) content in rabbit proximal tubular cells grown as a primary culture. 12-HETE 
      (1-10 microM) decreased [32P]PA content and stimulated [14C]DAG accumulation in a 
      concentration-dependent manner. The labeled phosphatidylcholine, 
      lysophosphatidylcholine, and sphingomyelin contents were not modified. 12-HETE 
      also decreased DAG kinase activity of cell membranes. 12-HETE (10 microM) 
      decreased the maximum velocity of Pi uptake by 36% and that of MGP uptake by 44% 
      but did not affect alanine uptake. The effect of 12-HETE on transport was 
      potentiated by calcium ionophore A23187 and was blunted by PKC downregulation. 
      The effects of 12-HETE on lipid composition and transport were mimicked by R 
      59022, a pharmacological DAG kinase inhibitor. Neither arachidonic acid nor 
      prostaglandin E2 reproduced the effects of 12-HETE. We conclude that in the 
      proximal tubule, 12-HETE affected Na-dependent Pi and MGP cotransport through 
      stimulation of PKC and that 12-HETE-induced activation of PKC is mediated by the 
      inhibition of DAG kinase.
FAU - Friedlander, G
AU  - Friedlander G
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) Unite 251, 
      Faculte de Medecine Xavier-Bichat, Universite Paris, France.
FAU - Le Grimellec, C
AU  - Le Grimellec C
FAU - Sraer, J
AU  - Sraer J
FAU - Amiel, C
AU  - Amiel C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Amino Acid Transport Systems)
RN  - 0 (Amino Acid Transport Systems, Neutral)
RN  - 0 (Carrier Proteins)
RN  - 0 (Diglycerides)
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (Phosphatidic Acids)
RN  - 0 (Sodium-Phosphate Cotransporter Proteins)
RN  - 0 (Symporters)
RN  - 0 (sodium-alanine cotransporter)
RN  - 59985-28-3 (12-Hydroxy-5,8,10,14-eicosatetraenoic Acid)
RN  - 9NEZ333N27 (Sodium)
RN  - EC 2.7.- (Phosphotransferases)
RN  - EC 2.7.1.107 (Diacylglycerol Kinase)
SB  - IM
MH  - 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
MH  - *Amino Acid Transport Systems
MH  - Amino Acid Transport Systems, Neutral
MH  - Animals
MH  - Carrier Proteins/*metabolism
MH  - Cells, Cultured
MH  - Diacylglycerol Kinase
MH  - Diglycerides/metabolism
MH  - Hydroxyeicosatetraenoic Acids/*pharmacology
MH  - Kidney Tubules, Proximal/cytology/*metabolism
MH  - Phosphatidic Acids/metabolism
MH  - Phosphotransferases/*antagonists & inhibitors
MH  - Sodium/metabolism
MH  - Sodium-Phosphate Cotransporter Proteins
MH  - *Symporters
EDAT- 1990/11/01 00:00
MHDA- 1990/11/01 00:01
CRDT- 1990/11/01 00:00
PHST- 1990/11/01 00:00 [pubmed]
PHST- 1990/11/01 00:01 [medline]
PHST- 1990/11/01 00:00 [entrez]
AID - 10.1152/ajprenal.1990.259.5.F816 [doi]
PST - ppublish
SO  - Am J Physiol. 1990 Nov;259(5 Pt 2):F816-22. doi: 
      10.1152/ajprenal.1990.259.5.F816.