Organic anion transporter protein inhibition

Organic anion transporter protein inhibition (OATP) - transports drugs into hepatocytes... 

There have been several studies that underscore the importance of unbound concentration in cell-based studies of receptor function. In a model study of the effect of plasma protein binding on the renal transport of organic anions using the expression of various organic anion transporters (OATPs) in Xenopus oocytes, the transport of ochratoxin A, methotrexate, and estrone sulfate was found to be strongly inhibited by the addition of human serum albumin to the culture medium [16]. Similarly, the addition of oq-acid glycoprotein was found to reverse the blockade of sodium-ion current by cocaine in a preparation of cardiac myocytes [17]. 

Vanadate transport in the erythrocyte was shown to occur via facilitated diffusion in erythrocyte membranes and was inhibited by 4,4 -diisothiocyanostilbene-2,2 -disulfonic acid (DIDS), a specific inhibitor of the band 3 anion transport protein [23], Vanadium is also believed to enter cells as the vanadyl ion, presumably through cationic facilitated diffusion systems. The divalent metal transporter 1 protein (called DMT1, and also known as Nramp2), which carries iron into cells in the gastrointestinal system and out of endosomes in the transferrin cycle [24], has been proposed to also transport the vanadyl cation. In animal systems, specific transport protein systems facilitate the transport of vanadium across membranes into the cell and between cellular compartments, whereas the transport of vanadium through fluids in the organism occurs via binding to proteins that may not be specific to vanadium. 

Cimetidine is a non-specific cytochrome P450 isoenzyme inhibitor, but it would seem that in most cases, with the exception of loratadine, these enzyme inhibitory effects do not significantly affect the metabolism of antihistamines. More recent evidence has shown cimetidine can also affect drug transporter proteins, in particular it may inhibit organic cation transporters. However, it probably does not affect anion transporter proteins since it does not affect the plasma pharmacokinetics of fexofenadine, which is a substrate of these transporters. ... 

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