Inhibitory effect on lithium on p-aminohippurate transport in rat kidney cortex in vitro.
The effect of lithium on p-aminohippurate (PAH) transport was studied using slices and basolateral membrane vesicles prepared from rat kidney cortex. The addition of lithium in concentrations ranging from 0.5 to 5 mM caused a concentration-dependent inhibition of PAH accumulation in the slices. Lithium inhibited PAH accumulation in the slices, not only during the rapid uptake period (after 10 min) but also during the approach to equilibrium (after 30 min). The effect of lithium (2 mM) in the slices was irreversible. The inhibitory effect of lithium was not the result of changes in the water distribution and the concentrations of ATP, sodium and potassium in the slices during incubation. The effect of lithium on the kinetic parameters for PAH accumulation was to decrease Vmax, while apparent Km remained constant. There was no lithium effect on the efflux of PAH from the slices back into the incubation medium, indicating that lithium inhibited PAH influx to the kidney cell. No evidence was obtained to indicate that lithium (1 mM) directly affected PAH uptake by isolated basolateral membrane vesicles. These results suggest that lithium seems to affect metabolism linked to the carriers for PAH transport other than ATP production and sodium gradient and then seems to decrease the mobility of the carriers in the membranes.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000618:Aminohippuric Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000618:Aminohippuric Acids; D000255:Adenosine Triphosphate; D008094:Lithium