Substrate-transporter interactions

The Local Environment Determines the Nature of Substrate-Transporter Interactions... 

Although both BBMECs and PBMECs are widely accepted as suitable in vitro models of the BBB, there are some limitations to the utility of these models. Over the years, the in vitro cell culture models have proven to be fairly reliable predictors of BBB permeability. However, as with any in vitro model, confirmation of results using an animal model is recommended. One should also be aware that substrate-transporter interactions have been shown to be altered in allelic variants... 

The antibiotics rifamycin SV and rifampicin reduce Sulfobromophthalein (BSP) elimination in humans. Using injected oocytes, Vavricka et al. (2002) demonstrated that rifampcin is transported by OATP-C and OATP8 and that both rifampicin and rifamycin SV inhibit OATP-C, 8, -B and -A mediated BSP uptake. These results show that rifamycin SV and rifampicin interact with OATP-mediated substrate transport to different extents. Inhibition of human liver OATPs can explain the previously observed effects of rifamycin S V and rifampicin on hepatic organic anion elimination. 

Drug-drug transport interactions are important in combinationtherapy with HIV protease inhibitors (117). Many protease inhibitors are substrates for and inhibitors of CYP3A4 and P-gp. Different combination effects (e.g./ intrinsic clearance of amprenavir is reduced by nelfinavir and indinavir but not saquinavir) depend on the extent to which one or both of these enzymes are affected. 

One of the innovative applications of scanning probe microscopy for nanolithography is dip pen nanolithography (DPN). In this special technique the water meniscus formed between the tip and the substrate acts as a medium for molecular transport. The technique depends on the key phenomenon that the molecule to be deposited on the substrate (which is referred as the ink ) can be transported in a controlled way from the tip (which is initially coated with the ink) to the substrate. The molecule (the ink) to be deposited on the substrate should interact with the substrate to form a chemical bond, leading to a stable structure [82]. 

In summary, ATP hydrolysis by P-gp correlates well with the intrinsic rate of substrate transport. A complete characterization of the interaction of a compound with P-gp is obtained by measuring the ATPase activity as a function of concentration. The rate of intrinsic substrate transport first increases with increasing concentration, reaches a maximum, and decreases again at high concentrations. The rate of intrinsic transport by P-gp depends not only on the substrate concentration but also on its affinity to the transporter substrates with high affinities for P-gp are transported more slowly than those with low affinities. 

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