Ryohei Hori

Transport of cephalosporin antibiotics in rat renal basolateral membranes

Abstract— Transport mechanisms of cephalosporin antibiotics in rat renal basolateral membranes have been studied in isolated membrane vesicles. Uptake of [14C]p‐aminohippurate, a typical organic anion, by basolateral membrane vesicles was enhanced when membrane vesicles were preloaded with unlabelled p‐aminohippur‐ate (counter‐transport). Cephalosporins such as cephradine, cephalexin, and cefazolin inhibited the counter‐transport of [14C]p‐aminohippurate, as did unlabelled p‐aminohippurate and probenecid. In contrast, cephalexin did not affect the uptake of [3H]tetraeth‐ylammonium, an organic cation, by basolateral membrane vesicles. These results suggest that most cephalosporins are transported via organic anion transport systems in rat renal basolateral membranes.

Decreased Transport of p-Aminohippurate in Renal Basolateral Membranes Isolated from Rats with Acute Renal Failure

Transport of D-glucose, p-aminohippurate (organic anion), and tetraethylammonium (organic cation) was studied in the renal basolateral membrane vesicles isolated from rats with acute renal failure (ARF). ARF was induced by a single injection of uranyl nitrate. Carrier-mediated transport of p-aminohippurate, estimated under anion–anion exchange condition, was significantly decreased in basolateral membrane vesicles isolated from ARF rats. In contrast, there were no significant differences in D-glucose and tetraethylammonium uptake between normal and ARF rats. When normal basolateral membrane vesicles were incubated in vitro with uranyl nitrate, no significant inhibition in p-aminohippurate uptake was observed. These results suggest that organic anion transport is decreased in renal basolateral membranes from ARF rats, and this transport dysfunction cannot be explained by the direct interaction of uranyl nitrate with the organic anion carrier.