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Vol. 61, Issue 5, 982-988, May 2002
Graduate School of Pharmaceutical Sciences, University of Tokyo,
Tokyo, Japan (Y.N., H.K., Y.S.); and Department of Pharmacology and
Toxicology, Kyorin University School of Medicine, Tokyo Japan (H.E.)
We reported previously that an efficient efflux system for
benzylpenicillin (PCG) is located on the choroid plexus (CP). In this
study, we investigated the involvement of rat organic anion transporter
1 (rOat1; Slc22a6) and rOat3 (Slc22a8) in
the uptake of PCG and p-aminohippurate (PAH) by the CP.
Western blot analysis indicates the expression of rOat3, but not rOat1,
on the CP, and immunohistochemical staining shows that rOat3 is
localized on the brush border membrane of the choroid epithelial cells.
PCG and PAH were found to be taken up by isolated rat CP, with
Km values of 111 and 354 µM, respectively.
A mutual inhibition study suggests that the same transporter is
responsible for the uptake of PCG and PAH by isolated rat CP. This was
confirmed by examining the effect of organic anions and cimetidine on
their uptake. Estradiol-17
-glucuronide and cimetidine were found to
be selective inhibitors of rOat3. The inhibition constants of the
inhibitors including estradiol-17-glucuronide and cimetidine were
comparable for the uptake of PAH and PCG by isolated rat CP. In
addition, these values were also comparable with those for rOat3, but
not with those for rOat1. These results suggest that rOat3 is mainly
responsible for the uptake of PCG and PAH by isolated rat CP, and it
functions as one of the detoxification systems on the CP by removing
its substrates from the cerebrospinal fluid.
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