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

dc.contributor.authorNopporn Apiwattanakulen_US
dc.contributor.authorTakashi Sekineen_US
dc.contributor.authorArthit Chairoungduaen_US
dc.contributor.authorYoshikatsu Kanaien_US
dc.contributor.authorNoriko Nakajimaen_US
dc.contributor.authorSamaisukh Sophasanen_US
dc.contributor.authorHitoshi Endouen_US
dc.contributor.otherKyorin University School of Medicineen_US
dc.contributor.otherMahidol Universityen_US
dc.description.abstractOrganic anion transporter 1 (OAT1) is the para-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 was trans-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.en_US
dc.identifier.citationMolecular Pharmacology. Vol.55, No.5 (1999), 847-854en_US
dc.rightsMahidol Universityen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectPharmacology, Toxicology and Pharmaceuticsen_US
dc.titleTransport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytesen_US