Uncouplers & pH

Jack Owicki jack_owicki at MOLDEV.COM
Wed Aug 7 11:05:38 EST 1996


Lou Hom wrote:
>Let's say you treat cells with an uncoupler of oxidative phosphorylation,
>like dinitrophenol (I think that's one), so that you cause the cell to burn
>up all kinds of fuel struggling to make some ATP.  Would you expect this to
>decrease the surrounding pH since more CO2 would be made?  Would you expect
>this in vivo too (for organisms as small as insects up to humans)?

We have in some cases seen increases in the extracellular acidification
rate of cells treated in vitro with uncouplers, using our microphysiometry
technology.  See, e.g., the effects of CCCP on P388D1 cells in Fig. 3 of
Parce et al. (1989) Science 246:243-247.

I would likely attribute this effect not just to the increase of CO2
production (like flooring the accelerator with the car in neutral), but
also to an increase in the excretion of lactic acid as glycolysis is
stimulated to make up the ATP deficit.

There may be other metabolic effects of increasing the proton permeability
of the plasma membrane and other intracellular membrane systems; I don't
believe that uncouplers are terribly selective.

Seems like similar things should happen in vivo, but I have no data on
that.  I do vaguely remember that DNP was used as an anti-obesity drug in
the early part of the century, one result being thermogenesis.

Jack.





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John C. Owicki, Ph.D.
Associate Technical Director & FLIPR Applications Manager
Molecular Devices Corporation
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