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9
The Kinetics
of Acetylcholinesterase Inhibition and the Influence
of Fluoride and Fluoride Complexes on the
Permeability of Erythrocyte Membranes - Page 9.
IV.
Conclusion
According to a theory of
Knappwost's, fluoride's protection against tooth
decay relies on a vagotonic influence on saliva
quantity and quality. Therefore, we looked for signs
of a vagotonic mechanism for the effect of fluoride.
On the basis of the inhibition of
acetylcholinesterase by fluoride we could show that
this inhibition increases when the pH is shifted
towards a more acidic level (up to pH 6-6.5).
Elucidating this state of affairs showed that the HF
molecule is the actual inhibitory agent. From this
it could be deduced that in those areas of the
organism where such pH shifts occur, an inhibition
of AChE is possible at physiological F
concentrations.
We could show that fluoride
complexes of Al and Si are only partially hydrolyzed
under "quasi physiological" conditions, and that in
the case of Si the "residual complexes" have an
inhibitory effect on AChE. The inhibitory capacity
of fluoride could be increased this way by using
fluorosilicates, which appear in the inanimate realm
of nature and probably also in the human body. Even
so called physiological fluoride concentrations
could now trigger vagotonic effects.
With the help of model
experiments on human red blood cells we could study
the influence of fluoride on the permeability of
erythrocyte membranes to electrolytes. We found that
the permeability for K+ and Ca2+
increases at fluoride concentrations over 10-4M.
In the case of Na+ permeability we could
already detect an impact at 5 x 10-5 M
NaF. A spontaneous influx of Na+,
which showed a certain similarity to the
circumstances at nerve cells upon stimulation by
acetylcholine, occurred upon contact of erythrocytes
with fluoride concentrations of 10-4 M.
The Na+ that had penetrated began to be
transported back out of the cell after only two
minutes. The dependence of Na+
permeability on fluoride concentrations after a
reaction time of 2-4 minutes showed a maximum
permeability at 10-4 M NaF. The exchange
of radioactive phosphate at the erythrocyte membrane
was also already affected at concentrations between
5 x 10-5 M and 10-4 M NaF.
Phosphoglycerate accumulation and a decline in ATP
synthesis only developed above 2.5 x 10-3
M NaF.
With the help of radioactive
fluoride (18F) we could show that
fluoride exchange occurs very quickly at the
erythrocyte membranes. At fluoride concentrations of
2.5 x 10-4 M the cells received half as
much 18F as the serum.
Altogether these studies suggest
that an effect of fluoride on the membrane
permeability for the aforementioned cations can
already develop at physiological F concentrations.
This is especially true for sodium. If these studies
can also be applied to other body cells (for example
nerve cells), it would mean that fluoride could, by
way of a slight rise in the "leaking flow" of K+
and especially Na+, affect the resting
potential, and thereby the overall excitability, of
the cells.
V.
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Introduction |
Contents |
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2 |
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7 |
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