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Schlagwörter:
SITS; Probenecid; Phloretin; Acetazolamide; Lactate; Renal tubule
Zusammenfassung:
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 actlac ). 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 (Jbblac ) and one going the paracellular pathway (J paracelllac =P lac·c lac lumen). Both, J actlac and J bblac of d-lactate gave the same Km 1.9 and 1.7 mmol/l and the same maximal transport rate 3.2 and 2.9 pmol cm−1 s−1. The Ki of l-lactate tested against J actlac and J bblac of d-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 that d-lactate uses the same transport system as l-lactate.
When Na+ was omitted from the perfusates J actlac disappeared completely, while J bblac was reduced by 64%. These data reflect the Na+ dependence of the d-lactate transport through the brush border. Variation of intra-and extracellular pH by raising p CO2, omitting HCO−3 from the perfusates or adding acetazolamide had no effect on the transport of d-lactate when α-keto glutarate was used as fuel. However, when acetate was used as fuel, intracellular acidosis brought the reduced J actlac 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) inhibited J actlac significantly. J bblac, 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) augmented J bblac 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 influence J bblac .
