Secretion of urate in the proximal convoluted tubule of the rat

In order to examine the transepithelial secretory flux of urate in the rat proximal tubule, simultaneous perfusions of capillaries and lumens were performed. The capillary perfusate contained [2-¹⁴C]urate in concentrations of 0.305-2.941 mM. The secretory flux of urate increased as the concentration of urate in the capillary perfusion solution was increased from 0.305 to 1.235 mM but tended toward a plateau at higher concentrations. An apparent Km of 0.41 mM and Vmax of 4.7 pmol·min^-1·mm^-1 were calculated from the observed net flux and an estimated passive permeability coefficient of 0.725 pmol·min^-1·mm^-1. The addition of probenecid (10^-4 M) to the capillary perfusion solution inhibited urate secretion in a manner consistent with that of a competitive inhibitor. The addition of p-chloromercuribenzoate (10^-4 M) to the capillary perfusion solution inhibited the Vmax but not the Km, suggesting a noncompetitive type of inhibition. These data provide the first estimates of the apparent transport constants for urate secretion in the rat proximal tubule determined in vivo. Urate secretion is mediated by a saturable carrier-mediated system. This carrier is not affected by the presence or absence of potassium in the perfusion solution but can be inhibited by the addition of either probenecid or p-chloromercuribenzoate.