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KMID : 0606320020180010031
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Journal of Phamacetical Sciences Sookmyung Women s University
2002 Volume.18 No. 1 p.31 ~ p.40
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The Mechanism of Blood-Brain Barreir Transport System of Organic Anion Drugs, Digoxin and Benzylpenicillin, Evaluated by Internal Carotid Artery Perfusion Method
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Kang Young-Sook
Lee Kyoung-Min
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Abstract
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Recently multispecific organic anion transporting polypeptides (oaths; oatpl, oatp2, oatp3) have been isolated fiom rat brain. Although these localizations at brain have been found that oath 1 situated at apical plasma membrane of choroid plexus, oatp2 located at basolateral cells pole of choroid plexus and endothelial cells of blood- brain barrier (BBB), there were no in vivo evidences about the localization of oatp2. On the purpose of evaluating in vivo evidences that oatps are located at BBB, an in situ rat brain perfusion technique was performed by time courses 15 sec, 1 min (4 ml/min) and 5 min (1.25 ml/min) with using some organic anions such as [3H]digokin, [3H]ouabain and [3H] benzylpenicillin, respectively and with efflux inhibitors such as verapamil or taurocholate sodium. In the case of digoxin, brain uptake of [3H]digokin (brawl volume of distribution, [VD] was higher than [VD] of [3H]ouabain (less than 2.0μg) and the effect of adding an efflux inhibitor, verapamil, was remarkable. Also, in the case of benzylpenicillin, the value of [VD] of [3H]benzylpenicillin when perfused with unlabelled benzylpenicillin (at 1 Mm of benzylpenicillin) showed higher (29.1 ± 2.9 μg) than [VD] of [3H]benzylpenicillin alone (21.7 ± 1.7μg) and the BBB permeability- surface area product (PS) of [3H]benzylpenicillin was significantly increased to 1.5 fo1d when perfused with verapamil or taurocholate sodium, respectively. These results suggest in vivo evidences of the presence of oaths and the effluutransport relationship at the BBB.
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