Demonstration of a Na(+)-dicarboxylate cotransporter in bovine adrenocortical cells.
Our study found the uptake of [14C]succinate into bovine adrenocortical cells to be sodium-dependent, inhibited by lithium, and to have an apparent K(m) of 146 mumol/l. Succinate uptake was inhibited by glutarate, fumarate, alpha-ketoglutarate, and maleate but not by 2,3-dimethylsuccinate or cis-aconitate, specific inhibitors of the basolateral Na(+)-dicarboxylate transporter of renal proximal tubule cells. Succinate uptake was highest at pH 6.0 and decreased with increasing pH. Transport of succinate was not significantly inhibited by citrate at pH 7.4 whereas at pH 6.0 inhibition of succinate uptake by citrate was small but significant. The affinity of the adrenal dicarboxylate transporter towards succinate ranges in between the low affinity of the renal luminal dicarboxylate transporter and the high affinity of the respective basolateral transporter. The pH dependency of succinate uptake and the missing inhibition by citrate at pH 7.4 differ from both the luminal and from the basolateral dicarboxylate transporters in kidney, liver, intestine, and placenta. These functional characteristics provide evidence for the existence of a Na(+)-dicarboxylate cotransporter in adrenocortical cells which may supply cholesterol metabolism with reducing substrates.
Steffgen
J
J
Abteilung Nephrologie und Rheumatologie, Georg-August-Universität Göttingen, Germany. jsteffgen@veg-physiol.med.uni-goettingen.de
Tolan
D
D
Beéry
E
E
Burckhardt
G
G
Müller
G A
GA
D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019343:Citric Acid / Q000494:pharmacology; D029382:Dicarboxylic Acid Transporters; D006863:Hydrogen-Ion Concentration; D008094:Lithium / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D008745:Methylation; D029363:Organic Anion Transporters, Sodium-Dependent; D012964:Sodium / Q000494:pharmacology; D013386:Succinates / Q000378:metabolism / Q000494:pharmacology; D019802:Succinic Acid / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D027981:Symporters
D002352:Carrier Proteins; D029382:Dicarboxylic Acid Transporters; D008565:Membrane Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; C092524:SLC13A2 protein, human; D013386:Succinates; D027981:Symporters; C042460:sodium-succinate-cotransporter; D019343:Citric Acid; D008094:Lithium; D012964:Sodium; D019802:Succinic Acid