Reabsorption of monocarboxylic acids in the proximal tubule of the rat kidney

Abstract

The transport ofd-lactate across the epithelium of the late proximal convolution was investigated by two methods: 1. by measuring the zero net flux transtubular concentration difference (Δc _tt,45s) and the permeability (P) ofd-lactate and calculating from both the transtubular active transport rate (J ^act_lac ). 2. By measuring the 3.5 s efflux ofd-lactate from the tubular lumen, while blood was flowing through the capillaries. The 3.5 s efflux comprises two components, one going through the brush border (J ^bb_lac ) and one going the paracellular pathway (J ^paracell_lac =P _lac·c _{lac lumen}). Both,J ^act_lac andJ ^bb_lac ofd-lactate gave the sameK _m 1.9 and 1.7 mmol/l and the same maximal transport rate 3.2 and 2.9 pmol cm⁻¹ s⁻¹. TheK _i ofl-lactate tested againstJ ^act_lac andJ ^bb_lac ofd-lactate was also the same: 1.1 and 1.0 mmol/l. These data indicate that under our experimental conditions only the flux through the brush border seems to be rate limiting and thatd-lactate uses the same transport system asl-lactate.

When Na⁺ was omitted from the perfusatesJ ^act_lac disappeared completely, whileJ ^bb_lac was reduced by 64%. These data reflect the Na⁺ dependence of thed-lactate transport through the brush border. Variation of intra-and extracellular pH by raisingpCO₂, omitting HCO ⁻₃ from the perfusates or adding acetazolamide had no effect on the transport ofd-lactate when α-ketoglutarate was used as fuel. However, when acetate was used as fuel, intracellular acidosis brought the reducedJ ^act_lac back to the values obtained with α-ketoglutarate as fuel. It is suggested that this is an effect on a contraluminal transport step.

Probenecid (5 mmol/l) and phloretin (0.25 mmol/l) inhibitedJ ^act_lac significantly.J ^bb_lac , however, was only inhibited by probenecid when acetate was used as fuel. These data indicate that both compounds act on thed-lactate exit at the contraluminal cell side, but that probenecid acts in addition at the luminal cell side. SITS (1 mmol/l) augmentedJ ^bb_lac when acetate was used as fuel and is similar to the effect of lowering intracellular pH as described above. The SH reagents mersalyl (1.0 mmol/l) and maleolylglycine (1 mmol/l) did not influenceJ ^bb_lac .