Compound profiling for P-glycoprotein at the blood-brain barrier using a microplate screening system
We isolated porcine brain capillary endothelial cells (PBCECs) and cultured them in 96-well plates. Cells were incubated with calcein-AM in the absence and presence of substrates and inhibitors of ABC transporters and the extent of intracellularly appearing fluorescence was monitored with a fluorescence plate reader in a time-and a concentration-dependent manner. PBCECs showed stable expression […]
Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice
We characterized the interaction of sulfasalazine, a substrate of the mouse ATP binding cassette drug transporter (ABCG2), with human ABCG2, via photoaffinity labeling with [125I]-iodoarylazidoprazosin. In addition, the inhibitory effect of curcumin on ABCG2 was evaluated in brain capillaries from rats. Furthermore, the effect of curcumin on absorption of orally administered sulfasalazine in wild-type and […]
Participation of monocarboxylate transporter 8, but not P-glycoprotein, in carrier-mediated cerebral elimination of phenytoin across the blood-brain barrier
Intracerebral pre-administration of unlabeled phenytoin attenuated blood-brain barrier (BBB)-mediated phenytoin efflux transport. Preadministration of P-glycoprotein (P-gp) substrates in rats and genetic P-gp deficiency in mice did not affect BBB-mediated phenytoin efflux transport. In contrast, pre-administration of monocarboxylate transporter-8 (MCT8) inhibitors attenuated phenytoin efflux. Our data suggest that MCT8 at the BBB participates in phenytoin efflux […]