DRUG TRANSPORT IN THE KIDNEY - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 469

Lumen

Blood

OAs

OATP1

G SH

OAs

OAT-Ks

OAs

DCs

H +

PEPT1/2

OAT1/3

Peptides

OAs

Na +

CNT1/2

Nucleosides

OAT2 OAs

DCs

OAT4
Oat5

OAs

MCs

Digoxin

OATP4C1

URAT1

Urate

OATv1
NPT1

OAs

ATP

OAs

MRP2/4

OCs

OCT2

ADP

OCs

OCs

OCT3

MATE1

H +

?

ATP

OCs

MDR1

ADP

FIGURE 15.1. Proposed model of organic anion and cation transporters in renal proximal
tubules. OAs, organic anions; OCs, organic cations; DCs, dicarboxylates; MCs, monocarboxy-
lates.

the functional properties and localization of OAT1 are identical to those of the
renal PAH transport system. The alternative splice variants of human OAT1 have
been identified 27 , 28 ; OAT1-1 and OAT1-2 appear to be functionally almost identical,
whereas no functions have been detected for OAT1-3 and OAT1-4. 29

OAT2 OAT2 was originally isolated from the rat liver as a novel liver-specific trans-
port protein with an unknown function. 30 Because of its structural similarities to
OAT1, OAT2 was functionally characterized. 31 OAT2 is expressed predominantly in
the liver and weakly in the kidneys. The typical substrates of OAT2 are salicylate,
acetylsalicylate, prostaglandin E 2 (PGE 2 ), dicarboxylates, PAH, zidovudine (AZT),
and tetracycline. 32-37

OAT3 OAT3 was isolated from the rat, 38 and it seems to us structurally identical to
Roct, which has been identified as a transporterlike protein that exhibits a reduced
expression in osteosclerosis mice. 39 OAT3 mRNA is expressed in the kidneys, liver,
brain, and eye. 38 In the kidneys, OAT3 is localized at the basolateral membrane of the