Roles of organic anion transporters in the renal excretion of perfluorooctanoic acid.
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 [(14)C] perfluorooctanoic acid transport activities. Both human and rat OAT1 and OAT3 mediated perfluorooctanoic acid transport to similar degrees. Specifically, the kinetic parameters, K(m), were 48.0 +/- 6.4 microM for h OAT1; 51.0 +/- 12.0 microM for rOAT1; 49.1 +/- 21.4 microM for hOAT3 and 80.2 +/- 17.8 microM 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.
Nakagawa
Hatsuki
H
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Hirata
Taku
T
Terada
Tomohiro
T
Jutabha
Promsuk
P
Miura
Daisaku
D
Harada
Kouji H
KH
Inoue
Kayoko
K
Anzai
Naohiko
N
Endou
Hitoshi
H
Inui
Ken-Ichi
K
Kanai
Yoshikatsu
Y
Koizumi
Akio
A
D000818:Animals; D001692:Biological Transport; D002210:Caprylates / Q000493:pharmacokinetics* / Q000652:urine*; D002460:Cell Line; D005466:Fluorocarbons / Q000493:pharmacokinetics* / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism; D027362:Organic Anion Transport Protein 1 / Q000235:genetics / Q000502:physiology*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000502:physiology*; D051381:Rats; D013045:Species Specificity; D014162:Transfection
D002210:Caprylates; D005466:Fluorocarbons; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; C490280:SLC22A7 protein, human; C421043:Slc22a6 protein, rat; C088800:Slc22a7 protein, rat; C114338:organic anion transport protein 3; C023036:perfluorooctanoic acid