Roles of Organic Anion Transporters in the Renal Excretion of Perfluorooctanoic Acid
Hatsuki Nakagawa
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto,
Search for more papers by this authorTaku Hirata
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, and
Search for more papers by this authorTomohiro Terada
Department of Pharmacy, Kyoto University Hospital, Kyoto, Japan
Search for more papers by this authorPromsuk Jutabha
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, and
Search for more papers by this authorDaisaku Miura
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, and
Search for more papers by this authorKouji H. Harada
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto,
Search for more papers by this authorKayoko Inoue
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto,
Search for more papers by this authorNaohiko Anzai
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, and
Search for more papers by this authorHitoshi Endou
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, and
Search for more papers by this authorKen-ichi Inui
Department of Pharmacy, Kyoto University Hospital, Kyoto, Japan
Search for more papers by this authorYoshikatsu Kanai
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, and
Search for more papers by this authorAkio Koizumi
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto,
Search for more papers by this authorHatsuki Nakagawa
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto,
Search for more papers by this authorTaku Hirata
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, and
Search for more papers by this authorTomohiro Terada
Department of Pharmacy, Kyoto University Hospital, Kyoto, Japan
Search for more papers by this authorPromsuk Jutabha
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, and
Search for more papers by this authorDaisaku Miura
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, and
Search for more papers by this authorKouji H. Harada
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto,
Search for more papers by this authorKayoko Inoue
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto,
Search for more papers by this authorNaohiko Anzai
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, and
Search for more papers by this authorHitoshi Endou
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, and
Search for more papers by this authorKen-ichi Inui
Department of Pharmacy, Kyoto University Hospital, Kyoto, Japan
Search for more papers by this authorYoshikatsu Kanai
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, and
Search for more papers by this authorAkio Koizumi
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto,
Search for more papers by this authorAbstract
Abstract: Perfluorooctanoic acid, an environmental contaminant, is found in both wild animals and human beings. There are large species and sex differences in the renal excretion of perfluorooctanoic acid. In the present study, we aimed to characterize organic anion transporters 1–3 (OAT1–3) in human beings and rats to investigate whether the species differences in the elimination kinetics of perfluorooctanoic acid from the kidneys can be attributed to differences in the affinities of these transporters for perfluorooctanoic acid. We used human (h) and rat (r) OAT transient expression cell systems and measured the [14C] perfluorooctanoic acid transport activities. Both human and rat OAT1 and OAT3 mediated perfluorooctanoic acid transport to similar degrees. Specifically, the kinetic parameters, Km, were 48.0 ± 6.4 µM for h OAT1; 51.0 ± 12.0 µM for rOAT1; 49.1 ± 21.4 µM for hOAT3 and 80.2 ± 17.8 µM for rOAT3, respectively. These data indicate that both human and rat OAT1 and OAT3 have high affinities for perfluorooctanoic acid and that the species differences in its renal elimination are not attributable to affinity differences in these OATs between human beings and rats. In contrast, neither hOAT2 nor rOAT2 transported perfluorooctanoic acid. In conclusion, OAT1 and OAT3 mediated perfluorooctanoic acid transport in vitro, suggesting that these transporters also transport perfluorooctanoic acid through the basolateral membrane of proximal tubular cells in vivo in both human beings and rats. Neither human nor rat OAT2 mediated perfluorooctanoic acid transport. Collectively, the difference between the perfluorooctanoic acid half-lives in human beings and rats is not likely to be attributable to differences in the affinities of these transporters for perfluorooctanoic acid.
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