Sodium Dicarboxylate Transporters in Placental Cells

Abstract

Placental cells express a number of transporters of metabolic substrates. To determine the presence and regulation of dicarboxylate transporters, we used an established human placental cell line, JAR. NaDC1 and −3 are respectively low and high affinity dicarboxylate transporters most studied on the apical and basolateral membranes of renal proximal tubule and intestinal cells.Both NaDC1 and −3 were present in JAR cells by immunohistochemistry and immunobloting; in the latter, patterns and levels were similar to cultured kidney cells. In JAR cells, 14C‐succinate (Succ) uptake averaged 5.1 ± 0.1 pMol/well and increased to 6.3 ± 0.2 (p < 0.05) by lowering Ca2+ to μM levels. Succ uptake was also stimulated (to 6.5 ± 0.2) by exposure to an acid media (pH ~ 7.1) for 48 h; Succ transport after acidosis was not Ca2+ sensitive. 14C‐Citrate (Cit) transport averaged 6.9 ± 0.5 but was not stimulated by either condition. Substrate affinities for Succ and Cit were relatively low, more consistent with NaDC1 than NaDC3.The stimulation of Succ but not Cit transport by acute reduction in extracellular Ca2+ or prolonged acid media contrasts with prior findings of ours with several kidney cell lines. The complex pattern of regulation suggests the presence of multiple dicarboxylate transporters in these cells with distinct regulation. In conclusion, placental cells contain both NaDC1 and −3, and transport Succ and Cit, but with distinct patterns of regulation. Because Cit complexes Ca2+, regulation of Cit transport could be involved in the placental calcification which occurs late in pregnancy. Funding VA, NIH.