Uncouplers selectivity

Reaction and Transport Interactions. The importance of the various design and operating variables largely depends on relative rates of reaction and transport of reactants to the reaction sites. If transport rates to and from reaction sites are substantially greater than the specific reaction rate at meso-scale reactant concentrations, the overall reaction rate is uncoupled from the transport rates and increasing reactor size has no effect on the apparent reaction rate, the macro-scale reaction rate. When these rates are comparable, they are coupled, that is they affect each other. In these situations, increasing reactor size alters mass- and heat-transport rates and changes the apparent reaction rate. Conversions are underestimated in small reactors and selectivity is affected. Selectivity does not exhibit such consistent impacts and any effects of size on selectivity must be deterrnined experimentally. 

The modes of action for niclosamide are interference with respiration and blockade of glucose uptake. It uncouples oxidative phosphorylation in both mammalian and taenioid mitochondria (22,23), inhibiting the anaerobic incorporation of inorganic phosphate into adenosine triphosphate (ATP). Tapeworms are very sensitive to niclosamide because they depend on the anaerobic metaboHsm of carbohydrates as their major source of energy. Niclosamide has selective toxicity for the parasites as compared with the host because Httle niclosamide is absorbed from the gastrointestinal tract. Adverse effects are uncommon, except for occasional gastrointestinal upset. 

The most probable mechanism for inverse agonism is the same one operable for positive agonism namely, selective receptor state affinity. However, unlike agonists that have a selectively higher affinity for the receptor active state (to induce G-protein activation and subsequent physiological response) inverse agonists have a selectively higher affinity for the inactive receptor state and thus uncouple already spontaneously coupled [RaG] species in the system. 

Liu H, Penner RM. 2000. Size-selective electrodeposition of mesoscale metal particles in the uncoupled limit. J Phys Chem B 104 9131-9139. 

Krupka, R. M., Uncoupled active transport mechanisms accounting for low selectivity in multidrug carriers P-glycoprotein and SMR antiporters,... 

While chronic morphine treatment uncouples the // receptor from K+ channels, it did not affect the coupling of ft receptors to adenylyl cyclase. Pretreatment of the cloned ft receptor expressed in HEK 293, AtT-20, CHO and COS cells with morphine or DAMGO for up to 16h did not alter the subsequent ability of fi agonists to inhibit cAMP accumulation [25, 65, 80-82]. These findings suggest that morphine treatment induces a selective desensitization of the coupling of the fi receptor to K+ channels. 

Wolff DJ, Mialkowski K, Richardson CF, Wilson SR (2001) C -fullerene monomalonate adducts selectively inactivate neuronal nitric oxide synthase by uncoupling the formation of reactive oxygen intermediates from nitric oxide production. Biochemistry 40 37 15. 

A different direction in ion-selective electrode research is based on experiments with antibiotics that uncouple oxidative phosphorylation in mitochondria [59]. These substances act as ion carriers (ionophores) and produce ion-specific potentials at bilayer lipid membranes [72]. This function led Stefanac and Simon to obtain a new type of ion-selective electrode for alkali metal ions [92] and is also important in supporting the chemi-osmotic theory of oxidative phosphorylation [69]. The range of ionophores, in view of their selectivity for other ions, was broadened by new synthetic substances [1,61]. 

They ion-selectively uncouple oxidative phosphorylation in mitochondria [115, 140], resulting in their bactericidal action [68]. 

Fig. 3. Signal transduction of the tt2A-D79N adrenergic receptor. Mutation of the aspartic acid residue 79 in the second transmembrane domain of the mouse a2A adrenergic receptor to asparagine (D79N) selectively uncoupled this receptor mutant from activation of currents in vitro without interfering with Ca channel or adenylyl cyclase inhibition (Surprenant et al. 1992). In vivo, the a2A D79N receptor was expressed at 20% of the level of the wild-type a2A-receptor (MacMillan et d. 1996), and Ca channel inhibition was also blunted (a) (Lakhlani et al. 1997)...

The deactivation kinetics were determined through a series of seven separate parameter estimation problems. As with the start-of-cycle case, separate estimating problems resulted from uncoupling the reactions of each carbon number by properly selecting the charge stock. This allowed the independent determination of submatrices in the rate constant matrix Dp [Eq. (37)]. 

On the other hand arrhythmia due to uncoupling may be prevented. If coupling is enhanced selectively in the previously uncoupled area only within that area cellular uncoupling would be antagonized, which means that the surrounding tissue would not be affected in the way described above. There might be a similar effect in the close border zone between diseased and normal tissue, but the effect would be confined to that zone. Inhomogeneities within the diseased zone would be smoothened whereas the normal tissue behavior would probably be less affected. This could especially smooth differences in action potential duration and thereby prevent, in some situations, from reentrant arrhythmia, since this is often related to differences in action potential duration, to dispersion. Another important factor in the initiation of reentry... 

Thus, enhancing intercellular coupling may exert a prophylactic effect against arrhythmia if arrhythmia is due to uncoupling. However, if the coupling effect is unselective, it would probably postpone an impairing effect as discussed above for ischemia. From this theoretical point of view selective couplingenhancing effects on the previously uncoupled tissue would be desirable rather than unselective. 

The control of lice, mites and warbleflies continues to be achieved by the older agents. The selection pressure that caused resistance in cattle ticks and sheep blowfly has not been encountered by these other ectoparasites since their less frequent incidence has required less insecticide/acaricide usage. In addition to the OPs, rotenone (92) (the active principle of derris), an uncoupler of oxidative phosphorylation, continues to be used to combat mange. 

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