Urate and p-aminohippurate transport in the brush border membrane of the pig kidney.
The transport of urate and p-aminohippurate (PAH) across the pig renal brush border membrane was investigated using membrane vesicles. Compared to a pH equilibrium condition (pHin = 7.4; pHout = 7.4), an outwardly directed OH- gradient (pHin = 7.4; pHout = 5.8) stimulated markedly both lactate and pyrazinoate uptake with overshoots exceeding 2 times that of the steady state. In contrast, neither OH-/urate nor OH-/PAH exchange could be demonstrated. An outwardly directed Cl- gradient (Cl-in = 100 mM; Cl-out = 16.7 mM) increased 2.6-fold 15-sec PAH uptake compared to Cl- equilibrium (Cl-in = Cl-out = 100 mM) but this stimulation was due solely to an effect of membrane potential. Creation of an electropositive intravesicular space, by imposing an inwardly directed K+ gradient (K+in = 0 mM; K+out = 100 mM) in the presence of valinomycin, was very effective to drive uphill PAH and urate accumulation compared to the control condition (no valinomycin). Four-second potential-stimulated PAH uptake was saturable (Km, 0.8 mM; Vmax, 1.7 nmol/mg of protein x 4 sec). Different organic anions cis-inhibited both 4-sec potential-stimulated PAH and urate uptakes in a similar fashion. PAH and urate, moreover, decreased each other's accumulation. In countertransport experiments, PAH and urate uptakes were not significantly stimulated by trans-unlabeled substrate. These results are consistent with the presence, in the pig renal brush border membrane, of a mediated secretory pathway common for urate and PAH, which could be facilitated by the potential difference existing in vivo across the luminal membrane of the proximal tubule.
Werner
D
D
Institut de Pharmacologie de l'Université, Lausanne, Switzerland.
Martinez
F
F
Roch-Ramel
F
F
D000618:Aminohippuric Acids / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport; D002712:Chlorides / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007773:Lactates / Q000493:pharmacokinetics; D019344:Lactic Acid; D008871:Microvilli / Q000378:metabolism; D013552:Swine; D014527:Uric Acid / Q000493:pharmacokinetics*; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics*
D000618:Aminohippuric Acids; D002712:Chlorides; D007773:Lactates; D014527:Uric Acid; D019344:Lactic Acid; D010130:p-Aminohippuric Acid