Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes

Organic anion transporter 1 (OAT1) is the para-aminohippurate (PAH) transpo rter in the basolateral membrane of the proximal tubule. The present study investigated whether or not nonsteroidal anti-inflammatory drugs (NSAIDs) a re transported by OAT1. All of the NSAIDs tested inhibited [C-14]PAH uptake via OAT1 expressed in Xenopus laevis oocytes. Ibuprofen, indomethacin, sal icylurate, and naproxen showed the strongest potency to inhibit [C-14]PAH u ptake (K-i similar to 2-10 mu M); acetylsalicylate, salicylate, and phenace tin exhibited moderate potency (K-i similar to 300-400 mu M), and acetamino phen (paracetamol) exhibited the weakest inhibitory potency (K-i similar to 2 m/M). Radiolabeled acetylsalicylate, salicylate, and indomethacin were t aken up by OAT1 and the uptake rate of these three NSAIDs was enhanced by t he outwardly directed dicarboxylate gradient. The efflux of the preloaded [ C-14]PAH from the oocytes via OAT1 was trans-stimulated by PAH and glutarat e added to the media. The addition of salicylate, acetylsalicylate, or sali cylurate into the media also trans-stimulated the efflux of PAH, whereas in domethacin did not. The present study indicates that OAT1 is responsible fo r the renal uptake and secretion of NSAIDs.