Inhibitory effect of unconjugated bilirubin on p-aminohippurate transport in rat kidney cortex slices

(1) The effects of unconjugated bilirubin on the accumulation of $\text{p-}\text{aminohippurate}$, kinetics of $\text{p-}\text{aminohippurate}$ uptake, the efflux of pre-accumulated $\text{p-}\text{aminohippurate}$ and water and electrolyte distribution were investigated in the rat kidney cortical slice. (2) The addition of unconjugated bilirubin to the incubation medium decreased the 60 min slice-to-medium concentration ratio of $\text{p-}\text{aminohippurate}$. (3) The decrease in $\text{p-}\text{aminohippurate}$ accumulation by unconjugated bilirubin was found to be more pronounced by increasing the concentration of pigment in the medium. (4) The rate of uptake of $\text{p-}\text{aminohippurate}$ as a function of $\text{p-}\text{aminohippurate}$ concentration differed in aerobiosis and anaerobiosis, and unconjugated bilirubin decreased only the uptake of $\text{p-}\text{aminohippurate}$ in aerobic conditions. (5) The efflux of pre-accumulated $\text{p-}\text{aminohippurate}$ decreased when unconjugated bilirubin concentration in the medium was low (10–20 μM) but the efflux increased when the concentration of pigment was much higher (100 μM). (6) The addition of unconjugated bilirubin to the medium (40–100 μM) increased intracellular sodium and total tissue water content, and decreased intracellular potassium and oxygen consumption of tissue. However the slices incubated with low concentration of pigment (20 μM) did not exhibit significative changes in cellular functional parameters. (7) These findings suggest that unconjugated bilirubin impairs $\text{p-}\text{aminohippurate}$ transport by a complex mechanism that might involve binding of pigment to sites necessary for anion transport, although effects related to pigment toxicity or to its oxidative decomposition are not excluded.