EXPRESSION OF A RENAL TYPE-I SODIUM PHOSPHATE TRANSPORTER (NAPI-1) INDUCES A CONDUCTANCE IN XENOPUS OOCYTES PERMEABLE FOR ORGANIC AND INORGANIC ANIONS/
Ae. Busch et al., EXPRESSION OF A RENAL TYPE-I SODIUM PHOSPHATE TRANSPORTER (NAPI-1) INDUCES A CONDUCTANCE IN XENOPUS OOCYTES PERMEABLE FOR ORGANIC AND INORGANIC ANIONS/, Proceedings of the National Academy of Sciences of the United Statesof America, 93(11), 1996, pp. 5347-5351
Two distinct molecular types (I and II) of renal proximal tubular brus
h border Na+/P-i cotransporters have been identified by expression clo
ning on the basis of their capacity to induce Na+-dependent P-i influx
in tracer experiments. Whereas the type II transporters (e.g., NaPi-2
and NaPi3) resemble well known characteristics of brush border Na+/P-
i cotransport, little is known about the properties of the type I tran
sporter (NaPi-1). In contrast to type II, type I transporters produced
electrogenic transport only at high extracellular P-i concentrations
(greater than or equal to 3 mM). On the other hand, expression of NaPi
-1 induced a Cl- conductance in Xenopus laevis oocytes, which was inhi
bited by Cl- channel blockers [5-nitro-2-(3-phenylpropylamino)benzoic
acid (NPPB) > niflumic acid >> 4,4'-diisothiocyanatostilbene-2,2'-disu
lfonic acid]. Further, the Cl- conductance was inhibited by the organi
c anions phenol red, benzylpenicillin (penicillin G), and probenecid.
These organic anions induced outwardly directed currents in the absenc
e of Cl-. In tracer studies, we observed uptake of benzylpenicillin wi
th a K-m of 0.22 mM; benzylpenicillin uptake was inhibited by NPPB and
niflumic acid. These findings suggest that the type I Na+/P-i cotrans
porter functions also as a novel type of anion channel permeable not o
nly for Cl- but also for organic anions. Such an apical anion channel
could serve an important role in the transport of Cl- and the excretio
n of anionic xenobiotics.