Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
Mol Pharmacol. 1999 May;55(5):847-54.
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 approximately 2-10 microM); acetylsalicylate, salicylate, and phenacetin exhibited moderate potency (Ki approximately 300-400 microM), and acetaminophen (paracetamol) exhibited the weakest inhibitory potency (Ki approximately 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.
有机阴离子转运体1（OAT1）是近端小管基底外侧膜中的对氨基马尿酸（PAH）转运体。本研究调查了非甾体抗炎药（NSAIDs）是否由OAT1转运。所有测试的NSAIDs均抑制通过非洲爪蟾卵母细胞中表达的OAT1摄取[14C]PAH。布洛芬、吲哚美辛、水杨尿酸和萘普生显示出最强的抑制[14C]PAH摄取的效力（Ki约为2 - 10 microM）；乙酰水杨酸、水杨酸和非那西丁表现出中等效力（Ki约为300 - 400 microM），而对乙酰氨基酚（扑热息痛）表现出最弱的抑制效力（Ki约为2 mM）。放射性标记的乙酰水杨酸、水杨酸和吲哚美辛被OAT1摄取，并且这三种NSAIDs的摄取速率因外向的二羧酸盐梯度而增强。预先加载的[14C]PAH从卵母细胞通过OAT1的流出受到添加到培养基中的PAH和戊二酸的反刺激。向培养基中添加水杨酸、乙酰水杨酸或水杨尿酸也反刺激了PAH的流出，而吲哚美辛则没有。本研究表明，OAT1负责NSAIDs的肾脏摄取和分泌。
