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...

Info

DISCOVERY OF THE ABCC MRP EFFLUX PUMPS AND GENOMIC ORGANIZATION OF THE ABCC GENES Tumor cell lines that have been made resistant to anticancer drugs by exposing them in vitro to increasing concentrations of a cytotoxic agent served as a valuable tool in the identification of the first ABCC MRP efflux pump. Studies with the doxorubicin-resistant cell lines HL60 ADR and H69AR revealed that both cell lines showed a multidrug resistance phenotype without overexpressing MDR1...

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...

Octn

Structure-Function Relationships Among the organic cation transporters, OCTN2 is identified as the most important carnitine transporter. Koepsell et al.5 have reviewed extensively the biochemistry and physiology of carnitine transport mediated by OCTN2 and other OCTN transporters. OCTN2 is a Na+ carnitine cotransporter with a high affinity for carnitine but can function alternatively as a polyspecific and Na+-independent cation uniporter.14-17 Na+-dependent transport of L-carnitine by OCTN2 is...

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...