T. Sekine et al., EXPRESSION CLONING AND CHARACTERIZATION OF A NOVEL MULTISPECIFIC ORGANIC ANION TRANSPORTER, The Journal of biological chemistry, 272(30), 1997, pp. 18526-18529
Numerous drugs and endogenous compounds are efficiently excreted from
the renal proximal tubule via carrier-mediated pathways. Transepitheli
al excretion of organic anions occurs via their accumulative transport
from the blood into the proximal tubule cells across the basolateral
membrane and subsequent secretion into the urine through the apical me
mbrane. Here we report on the isolation of a novel complementary DNA f
rom rat kidney that encodes a 551-amino acid residue protein (OAT1) wi
th 12 putative membrane-spanning domains. When expressed in Xenopus la
evis oocytes, OAT1 mediated sodium-independent para-aminohippurate (PA
H) uptake (K-m = 14.3 +/- 2.9 mu M). The uptake rate of PAH was increa
sed by the outwardly directed dicarboxylate gradient, consisting with
the idea that OAT1 is an organic anion/dicarboxylate exchanger, OAT1 d
isplayed remarkably wide substrate selectivity, covering endogenous su
bstrates such as cyclic nucleotides, a prostaglandin and uric acid, an
d a variety of drugs with different structures (e.g. antibiotics, a no
nsteroidal antiinflammatory drug, diuretics, an antineoplastic drug, a
nd a uricosuric drug). The Northern blot analysis and in situ hybridiz
ation revealed that OAT1 is exclusively expressed in the particular se
gment of the proximal tubule in the kidney. These data suggest that OA
T1 is a multispecific organic anion transporter at the basolateral mem
brane of the proximal tubule. Isolation of OAT1 will facilitate elucid
ation of the molecular basis of drug kinetics and the development of n
ew drugs lacking unwanted side effects.