Hydrocortisone upregulates organic anion (OA) transport in the opossum kidney (OK) cell line

Abstract

In rats and humans corticosteroids upregulate renal OA transport, but the mechanism of this upregulation has not been characterized. An increase in uptake may involve increasing capacity (Jmax) for, or affinity (Km) of substrate for a transporter. Here we characterized the effect of long-term (5 day) exposure to hydrocortisone on the basolateral membrane transport kinetics of p-aminohippurate (PAH) in OK cell cultures. Five-day treatment of OK cell cultures with 10 μM hydrocortisone produced a two-fold increase in PAH transport compared to ethanol-treated controls. The regulation of OA transport by treatment with 10 μM hydrocortisone was further characterized by measuring the kinetics of basolateral PAH uptake in OK cell cultures. The capacity for PAH uptake in OK cell cultures increased more than five-fold (ethanol-treated vs. hydrocortisone-treated, Jmax = 0.5 mol·cm−2·min−1 vs. 2.8 mol·cm−2min−1), whereas no significant change in the affinity for basolateral PAH uptake was observed (ethanol-treated vs. hydrocortisone-treated, Km = 71 vs. 123 μM). The marked increase in the Jmax for basolateral PAH uptake with minimal change in Km is consistent with an upregulation of OA transport protein expression. Thus, our data suggest long-term exposure to hydrocortisone may upregulate PAH transport by an increase in OA transporter protein expression. Supported by DK062097.