Uncouplers resistance

Uncoupling Resistances Use in Physiologically Based Pharmacokinetics Models and Cell Culture Analog Systems... 

A convenient method of carrying out such a galvanic test in the laboratory has been described by Wesley in which the vertical circular-path machine is used. Each assembly includes two pairs of dissimilar metals—one pair coupled galvanically while the other pair is left uncoupled in order to determine the normal corrosion rates under the same environmental conditions. The type of motion provided (specimens moving in a vertical circular path) enables electrical connections to be made without mercury cup or commutator and the leads can be connected to a calibrated resistance for current measurements attached to the specimen carrier. 

Liu, Y-Y., Han, T-Y., Giulano, A. E., Hansen, N., and Cabot, M. C., 2000, Uncoupling ceramide glycosylation by transfection of glucosylceramide synthase antisens reverses adiiamycin resistance. J. Biol. Chem. 275 7138-7143. 

Because rodent populations world-wide were becoming resistant to the widely used Warfarin-type anticoagulant poisons, a search was initiated to find a rodenticide with a different mode of action one that would be effective against these resistant rodents. This search led to the discovery of the toxic nature of a family of diphenyl amines which act as uncouplers of oxidative phosphorylation. A structure-activity relationship (SAR) study was undertaken to choose a derivative that would be both poisonous to rodents but still readily consumed by them. This approach led to the discovery of bromethalin,... 

In crayfish septate axon, a more complex action of lowering pH has been described [Peracchia, 1991a] superfusion with Na-acetate led to a rapid increase in junctional resistance (Rj) with a concomitant fall in pi (, but the recovery curve for pi f was slower than that for Rj. A concomitant increase in intracellular [Ca2+] was observed so that it was concluded that the pHj effect on cellular uncoupling in crayfish septate axon is mediated by calcium. Thus, generalizations of the various mechanisms should be avoided and the specific experimental model has to be taken into account. 

Acetylcholine is involved in many aspects of the regulation of the cardiovascular system. Thus, it may also play a role in the control of intercellular communication. Very early in gap junction research the effect of acetylcholine as an important transmitter on gap junction conductance has been investigated. First, Petersen and Ueda [1976] demonstrated an increase in junctional resistance in pancreatic acinar cells following the application of acetylcholine. Concomitantly, the release of amylase was stimulated. A minimum concentration of 1 pmol/l acetycholine was required to evoke uncoupling. The next question was, how is the acetylcholine effect mediated Calcium has been considered to contribute to the mechanism of action [Iwatsuki and Pertersen,... 

Kleber AG, Riegger CB, Janse MJ Electrical uncoupling and increase of extracellular resistance after induction of ischemia in isolated, arterially perfused rabbit papillary muscle. Circ Res 1987 61 271-279. 

Laties and associates589-592 provided evidence for an alternative, cyanide-resistant path of respiration in avocado mitochondria. Uncouplers were considered to stimulate glycolysis to the point where the glycolytic flux exceeds the oxidative capacity of the cytochrome pathway, with the result that the alternative pathway is engaged. However, these authors concluded that the alternative pathway is not required in order to sustain the elevated rate of respiration that characterizes the climacteric. Clarification of the role, if any, of this alternative pathway in fruit ripening awaits further study. 

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. 

It has been suggested that brown adipose tissue may also function to convert excess dietary fat into heat and thereby to resist obesity.k m Mice lacking the gene for the mitochondrial uncoupling protein are cold-sensitive but not obese. However, other proteins, homologous to UCP1, have been discovered. They may partially compensate for the loss.m,h... 

Hotamishgil, G S., et al., Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science, 1996, 274, 1377-1379. 

Consistent with an antifolding role, 25% of the preMBP trapped within secB null strains by the addition of the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) folds into a protease-resistant conformation, while in secB cells, only 5% folds (Kumamoto and Gannon, 1988). Given that protease resistance is a less sensitive probe of preMBP conformation than export competence [in vitro the translocation competence of preMBP decays more rapidly than its protease sensitivity (Weiss et al., 1989)], then this protease-resistant fraction and the fraction of preMBP that becomes export incompetent in secB null strains are quantitatively similar (25% vs. 40%, respectively). Hence the fraction of MBP that is unable to be translocated in the absence of SecB represents the folded fraction. 

Tphe search for insecticides with modes of action different from the A well-known acetylcholinesterase inhibition led us to uncouplers of oxidative phosphorylation (1, 2). An inherent advantage of such pesticides would be the absence of cross-resistance with organophosphorus compounds and chlorinated hydrocarbons. The number of commercial pesticides which are likely to act by uncoupling of oxidative phosphorylation is small. All of them can be regarded as derivatives of the... 

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