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Basolateral cell membrane; Methylsuccinate-transport; 2-Oxolutarate-transport; Citrate-transport; Lithium
Abstract:
The transport of dicarboxylic acids in the proximal convolution was investigated by measuring: a) the zero net flux transtubular concentration difference ofdl-methyl-succinate, b) its 2-s influx from the interstitium into tubular cells, and c) its 3.5-s efflux from the tubular lumen. With the first method a luminal concentration exceeding the peritubular concentration was observed, thus indicating a net active transtubular secretion of this slowly metabolized substance.
All transport steps, luminal and contraluminal, as well as the overall transport, were Na+-dependent and inhibited by lithium (apparent Ki ≈ 1.8 mmol/l). The overall transport of methylsuccinate, as well as the contraluminal influx into proximal tubular cells, could be inhibited by paraaminohippurate and H2-DIDS with an apparent Ki of ≈ 1.8 mmol/l, by taurocholate with an apparent Ki ≈ 3.` mmol/l and by pyruvate with an apparent Ki ≈ 5 mmol/l, but not by sulfate, thiosulfate, l-lactate, oxalate and urate. As judged from the inhibition of contraluminal methylsuccinate influx by 48 dicarboxylic acids (aliphatic and aromatic), a specificity pattern was observed similar to that of inhibition of luminal efflux of 2-oxoglutarate [22]: a preference of dicarboxylates in the transconfiguration with a chain length of 4–5 carbons; little change in the inhibitory potency with CH3−, OH−, SH−and O=, but strong reduction with a NH+3 in the 2 position; only a small reduction of inhibitory potency with 2,3 disubstituted SH and OH analogs; preference of the dicarboxylic benzene in the 1,4 position and of the diacetyl benzene in the 1,2 position. The data indicate a Na+-dependent dicarboxylic transport system at the contraluminal cell side of the proximal tubule which is very similar to the luminal transport system for dicarboxylic acids.
