Szwergold BS. Brown TR. Freed JJ.
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Bicarbonate abolishes intracellular alkalinization in mitogen-stimulated
Journal of Cellular Physiology. 138(2):227-35, 1989 Feb.
An increase in intracellular pH (pHi) following mitogenic stimulation
been reported in a variety of mammalian cells (W. Moolenaar, Annu.
Physiol., 48:363-376, 1986; E. Rozengurt, Science, 234:161-166, 1986).
increase is currently believed to constitute a "permissive" signal
process of cell activation (A.E. Lagarde and J.M. Pouyssegur, Cancer
Biochem. Biophys. 9:1-14, 1986). Since the majority of studies of this
phenomenon have been conducted in the nonphysiological milieu of
bicarbonate-free solutions, we have undertaken a study of the effects
bicarbonate and CO2 on mitogen-induced intracellular alkalinization
3T3 cells. Using nuclear magnetic resonance (NMR) spectroscopy and
NMR pH indicators (2-amino-phosphono-carboxylic acids) we found that
induces an increase in pHi of 0.16 units only in cells bathed in medium
containing low concentrations of bicarbonate (less than 1 mM) and not
cells bathed in medium containing physiological levels of bicarbonate
mM). In addition to abolishing the mitogen-induced alkalinization,
bicarbonate stabilizes pHi at 7.25 units as the external pH (pHe) is
from 7.0 to 7.6. In contrast, in a bicarbonate-free medium pHi increases
from 6.9 to 7.3 over the same range of external pHs. At a constant
pH, increasing the bicarbonate/CO2 concentration results in an increase
pHi from 6.9 in bicarbonate-free solution to 7.25 in a bicarbonate-buffered
medium. This relationship is hyperbolic with half-maximal effect occurring
at a concentration of 0.4 mM bicarbonate at pH 7.05 and 37 degrees
results suggest that the observations of mitogen-induced alkalinization
be due to the use of nonphysiological bicarbonate-free media. Since
increase in pHi is not observed in physiological media where bicarbonate
concentrations are usually greater than 20 mM, we conclude that an
in pHi is not an obligatory or usual part of the cellular response
factors in vivo.
Institute Bergonie, Bordeaux.
[Claude Lagarde]. [French]
Le professeur Claude Lagarde.
Bulletin du Cancer. 83(4):251-2, 1996 Apr.
NLM Journal Code
Country of Publication
MeSH Subject Headings
History of Medicine, 20th Cent
Radiotherapy / hi [History]
Personal Name as Subject
Biography. Historical Article. Journal Article.
Saludos realmente escépticos.