Dose-dependent binding

Figure 43 Folate targeted PAMAM dendrimers. Dose-dependent binding of G5-FI-FA-MTX in KB cells. The cells were maintained in FA-free medium and incubated with different concentrations of the indicated dendrimers for 1 h. The cells were then rinsed and resuspended in PBS buffer, and the fluorescence was measured in a flow cytometer (a). In panel b, the mean cell fluorescence, after being normalized for the fluorescence of standard solutions of the dendrimers, is presented. FA, folic acid MTX, methotrexate. FI, fluorescein isothiocyanate. Reproduced with permission from Thomas, T. P. Majoros, I. J. Kotlyar, A. etal. J. Med. Chem. 2005, 48, 3729 310 Copyright 2005 American Chemical Society.

Kautiainen A, Vogel JS, Turteltaub KW. Dose-dependent binding of trichloroethylene to hepatic DNA and protein at low doses in mice. Chem-Biol Interact 1997 106 (2) 109-121. 

Feverfew ethanolic extract demonstrated a significant dose-dependent binding affinity to the GABA(A)-benzodiazepine receptor. Parthenolide and feverfew extract have in vitro antiproliferative activities against a number of human tumor cell lines of lymphoma, breast, and cervical cancers. ... 

Hillefors-Berglund M, Liu Y, von Euler G Persistent, specific and dose-dependent effects of toluene exposure on dopamine D2 agonist binding in the rat caudate-putamen. Toxicology 77 223-232, 1993... 

The differences between palytoxin and PDBu with respect to kinetics, temperature dependence, and effect on low affinity binding suggest that these two different types of tumor promoters may be acting through different mechanisms. Further, in contrast to PDBu, the effect of palytoxin is not readily reversible (33). To determine where the two pathways differ, we compared the relative ability of palytoxin and PDBu to inhibit EGF binding in protein kinase C depleted cells. Swiss 3T3 cells were depleted of protein kinase C to different extents by exposing confluent quiescent cells to 0, 20, 200, or 2000 nM PDBu for 72 hr. Previous results indicate that this treatment depletes cells of protein kinase C activity in a dose-dependent manner (31). 

Because these results suggest that extracellular Na is required for inhibition of EGF binding by palytoxin in these cells, we determined if palytoxin caused Na influx in Swiss 3T3 cells. When Na influx was monitored at an early time point (7 min), it was found that palytoxin causes an influx of Na and that the rate of Na influx is dose dependent (Figure 6). In parallel with its effect on EGF binding, palytoxin at different doses increases intracellular Na to the same final level (42). Although Na influx occurs prior to the inhibition of EGF binding, these results and the apparent Na dependence of the palytoxin effect suggest a role for Na in the action of palytoxin on the EGF receptor. 

Protein binding No 75-90% 40% of active metabolite 80-90% (dose dependent) 55%... 

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