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Vol. 55, Issue 5, 847-854, May 1999
Department of Pharmacology and Toxicology, Kyorin University School
of Medicine, Tokyo, Japan (N.A., T.S., A.C., Y.K., N.N., H.E.); and
Department of Physiology, Faculty of Science, Mahidol University,
Bangkok, Thailand (N.A., S.S.)
Organic 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 (Ki ~ 2-10 µM); acetylsalicylate, salicylate, and phenacetin exhibited
moderate potency (Ki ~ 300-400 µM), and
acetaminophen (paracetamol) exhibited the weakest inhibitory potency
(Ki ~ 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.
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