Abstract

Organic anion transporter 1 (OAT1) is thepara-aminohippurate (PAH) transporter in the basolateral membrane of the proximal tubule. The present study investigated whether or not nonsteroidal anti-inflammatory drugs (NSAIDs) are transported by OAT1. All of the NSAIDs tested inhibited [¹⁴C]PAH uptake via OAT1 expressed in Xenopus laevis oocytes. Ibuprofen, indomethacin, salicylurate, and naproxen showed the strongest potency to inhibit [¹⁴C]PAH uptake (K_i∼ 2–10 μM); acetylsalicylate, salicylate, and phenacetin exhibited moderate potency (K_i ∼ 300–400 μM), and acetaminophen (paracetamol) exhibited the weakest inhibitory potency (K_i ∼ 2 mM). Radiolabeled acetylsalicylate, salicylate, and indomethacin were taken up by OAT1 and the uptake rate of these three NSAIDs was enhanced by the outwardly directed dicarboxylate gradient. The efflux of the preloaded [¹⁴C]PAH from the oocytes via OAT1 wastrans-stimulated by PAH and glutarate added to the media. The addition of salicylate, acetylsalicylate, or salicylurate into the media also trans-stimulated the efflux of PAH, whereas indomethacin did not. The present study indicates that OAT1 is responsible for the renal uptake and secretion of NSAIDs.