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Transport properties of 3′‐azido‐3′‐deoxythymidine and 2′,3′‐dideoxyinosine in the rat choroid plexus
Author(s) -
Takasawa Katsuko,
Suzuki Hiroshi,
Sugiyama Yuichi
Publication year - 1997
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199710)18:7<611::aid-bdd45>3.0.co;2-2
Subject(s) - choroid plexus , pharmacology , choroid , chemistry , medicine , biology , neuroscience , central nervous system , retina
Transport properties of 3′‐azido‐3′‐deoxythymidine (AZT) and 2′, 3′‐dideoxyinosine (DDI) were characterized in the isolated rat choroid plexus. AZT and DDI competitively inhibited the active transport of [ 3 H]benzylpenicillin, a prototypic organic anion, with K i values of 85·4±13·1 and 155±22 μM, respectively. Accumulation of [ 3 H]DDI was against an electrochemical potential via a saturable process ( K m =29·7±4·9 μM, V max =13·5±2·4 pmol min −1 /μL tissue) that was inhibited by metabolic inhibitors (carbonylcyanide p ‐trifluoromethoxyphenylhydrazone, 10 μM, and rotenone, 30 μM) and sulphydryl reagents ( p ‐chloromercuribenzoic acid, 100 μM, and p ‐chloromercuribenzenesulphonic acid, 100 μM), but did not require an inwardly directed Na + gradient. Accumulation of [ 3 H]DDI was inhibited by benzylpenicillin and AZT in a dose‐dependent manner, with IC 50 values of 91·6±28·9 and 294±84 μM, respectively. In contrast, no significant accumulation of [ 3 H]AZT was observed. These results suggest that DDI is transported, at least in part, by the transport system for organic anions located on the rat choroid plexus, whereas AZT is recognized, but not transported by this system. © 1997 John Wiley & Sons, Ltd.