References

P-glycoprotein structure and evolutionary homologies. Cytotechnology 12 1-32. 2. Lincke CR, Broeks A, The I, Plasterk RH, Borst P. 1993. The expression of two P-glycoprotein (pgp) genes in transgenic Caenorhabditis elegans is confined to intestinal cells. EMBO J 12 1615-1620. 3. Ruetz S, Gros P. 1994. Phosphatidylcholine translocase a physiological role for themdr2 gene. Cell 77 1071-1081. 4. Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC. 1987. Cellular...

Pglycoprotein As A Hydrophobic Vacuum Cleaner Or Drug Flippase

Pgp substrates are typically hydrophobic and are expected to partition into the membrane. The substrate-binding sites of Pgp appear to be contained within its TM regions, and drugs gain access to these sites after partitioning into the lipid bilayer (Figure 10.2a).34 The idea that the transporter acts as a vacuum cleaner for hydrophobic molecules present in the membrane was first suggested by Higgins and Gottesman149 and has found widespread acceptance. In intact cells, Pgp substrates entering...

Clinical Applications And Implications For Drug Delivery

Natural Substrates MCT1-4 and SMCTs 1 and 2 are known to transport a variety of physiologically relevant substrates, including lactate, pyruvate, and butyrate. Each of these monocarboxylate transporters exhibits unique kinetic properties. The affinity for monocarboxylates by MCT1 and MCT4 is very similar across species, while the affinity for monocarboxylates by MCT2 varies greatly between rodents and humans (Table 7.1). Rat MCT2 was characterized as the high-affinity pyruvate carrier because...

Substrate Specificity Of Pglycoprotein And Nature Of The Drugbinding Site

Pgp displays a remarkable ability to interact with, and transport, a large variety of compounds, ranging from chemotherapeutic drugs to peptides. Most preferred substrates are amphipathic and relatively hydrophobic, although some are not colchicine, for example, is quite water soluble . Pgp substrates range in size from large complex molecules such as paclitaxel and vinblastine to smaller drugs such as daunorubicin and doxorubicin. Pgp also interacts with linear and cyclic peptides and...