Clinical Significance Of Nucleoside Transporters

The clinical significance of nucleoside transporters can be viewed in several aspects. First, a number of anticancer nucleoside analogs rely on nucleoside transporters to enter cells to reach their cellular targets. As such, the expression level of nucleo-side transporters on the target cells is an important determinant for intracellular drug bioavailability, and consequently, responsiveness to therapy. Second, if a drug is a substrate for nucleoside transporters, the distribution of these...

Mct6

A N.A., not available. bKm value (mM). a N.A., not available. bKm value (mM). are the flavonoids phloretin and quercetin. The hystidyl-selective reagent diethyl pyrocarbonate (DEPC) is the only compound known to inhibit MCT3. Treatment with hydroxylamine did not reverse the inhibition therefore, the authors concluded that DEPC inhibition was caused by modification of lysine or arginine residues.54 Interestingly, MCT3 was found to be insensitive to the classical MCT inhibitors, such as...

Enterohepatic Bile Acid Transporters In Liver Disease

Chronic cholestatic liver diseases such as primary biliary cirrhosis and primary sclerosing cholangitis are characterized by an impairment of bile formation or of bile flow. Altered expression or function of bile acid transporters can be either a cause or a consequence of cholestasis, thus leading to hepatotoxicity due to accumulation of bile acids and cholephilic toxins in hepatocytes. Among the genes encoding transporters that are involved in bile acid transport or bile formation are several...

Molecular And Structural Characteristics

Adrenal Vasculature

Members of the POT superfamily share a common topological map consisting of 12 putative a-helical transmembrane domains with intracellularly localized N- and C-termini.13'22'23 Two characteristic protein signatures of the POT family members have been identified, known as the PTR2 family signatures (1) and (2) A FIGURE 6.1. Potential parallel or competing pathways available for oligopeptide and peptide-based drug permeation and their potential intracellular fates across cellular barriers....

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...

Abcc1

The ABCC1 protein is detectable in a number of human cells and tissues with the highest levels in lung, testis, kidney, and macrophages.17-174 Normal human hepatocytes lack detectable amounts of ABCC1,159-175 but ABCC1 seems to be up-regulated in proliferating hepatocyte-derived cells.175 Immunohistochemical and immunoflu-orescence analyses have shown that ABCC1 is localized predominantly in cells of blood-tissue barriers which form pharmacological sanctuaries in the body. ABCC1 is, for...