BACKGROUND AND PURPOSE Brain arteries are structurally characterized by the tight junctions of the endothelium and by no vasa vasorum that feed arteries themselves. This raises the question of how brain arteries are provided with glucose. A possible explanation is that glucose uptake into arteries may be mediated by both GLUT1, a facilitative glucose transporter, and a Na+/glucose cotransporter...

The anion transport inhibitor DIDS is known to reduce aqueous humor secretion but questions remain about anion dependence of the effect. In some tissues, DIDS is reported to cause Na-K-ATPase inhibition. Here, we report on the ability of DIDS to inhibit Na-K-ATPase activity in nonpigmented ciliary epithelium (NPE) and investigate the underlying mechanism. Porcine NPE cells were cultured to conf...

Intrinsic sensitivity of newly diagnosed chronic myeloid leukemia (CML) patients to imatinib (IC50(imatinib)) correlates with molecular response. IC50(imatinib) is defined as the in vitro concentration of drug required to reduce phosphorylation of the adaptor protein Crkl by 50%. We now show that interpatient variability in IC50(imatinib) is mainly due to differences in the efficiency of imatin...

The effect of the nephrotoxic aminoglycoside antibiotic, gentamicin, on calcium uptake by renal cortical mitochondria was assessed in vitro. Gentamicin was found to be a competitive inhibitor of mitochondrial Ca++ uptake. This effect displayed a dose response with a Ki of 233 microM and occurred at gentamicin concentrations below those that inhibit mitochondrial electron transport. These result...

Here, we report that Cdk5 activation is stimulated by insulin and plays a key role in the regulation of GLUT4-mediated glucose uptake in 3T3-L1 adipocytes. Insulin activation of Cdk5 requires PI3K signaling. Insulin-activated Cdk5 phosphorylates E-Syt1, a 5 C2-domain protein-related to the synaptotagmins that is induced during adipocyte differentiation. Phosphorylated E-Syt1 associates with GLU...

The effect of inhibitors and intermediates of heme synthesis, inhibitor of globin synthesis, and some iron proteins on in vitro iron uptake and haemoglobin synthesis by reticulocytes of iron deficient subjects was investigated in this study. Lead, INH, ALA, mesoprophyrin, ferritin and albumin substantially increased iron uptake by iron deficient reticulocytes, while cycloheximide and glycine de...

The involvement of cytosolic phospholipase A(2) (cPLA(2)) and ceramide in the accumulation of cholesteryl ester induced by the uptake of oxidized low-density lipoproteins (oxLDL) in macrophages was investigated. Uptake of oxLDL by [(3)H]oleic acid-labeled macrophages stimulated the formation of cholesteryl oleate, and this process was completely inhibited by a cPLA(2) inhibitor. Under the condi...

not rely on OCT1 transporter activity. Functional OCT1 activity was determined by subtracting the uptake in the presence of amantadine, a specific OCT1 inhibitor according to the authors, from the uptake observed in unmanipulated cells. Examination of the data presented in their Figure 2 suggest that the IUR of imatinib in the absence of 500 mM of amantadine was increased by;50% in OCT1-transfe...

Intrinsic sensitivity of newly diagnosed chronic myeloid leukemia (CML) patients to imatinib (IC50imatinib) correlates with molecular response. IC50imatinib is defined as the in vitro concentration of drug required to reduce phosphorylation of the adaptor protein Crkl by 50%. We now show that interpatient variability in IC50imatinib is mainly due to differences in the efficiency of imatinib int...

Lapatinib [N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine, GW572016, Tykerb] is a tyrosine kinase inhibitor approved for use in combination with capecitabine to treat advanced or metastatic breast cancers overexpressing HER2 (ErbB2). In this work we investigated the role of efflux and uptake transporters in lapatinib dispositi...