Unique Identifier
89139593
Authors
Szwergold BS. Brown TR. Freed JJ.
Institution
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Title
Bicarbonate abolishes intracellular alkalinization in mitogen-stimulated
3T3
cells.
Source
Journal of Cellular Physiology. 138(2):227-35, 1989 Feb.
Abstract
An increase in intracellular pH (pHi) following mitogenic stimulation
has
been reported in a variety of mammalian cells (W. Moolenaar, Annu.
Rev.
Physiol., 48:363-376, 1986; E. Rozengurt, Science, 234:161-166, 1986).
This
increase is currently believed to constitute a "permissive" signal
in the
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
of
bicarbonate and CO2 on mitogen-induced intracellular alkalinization
in NIH
3T3 cells. Using nuclear magnetic resonance (NMR) spectroscopy and
novel 31P
NMR pH indicators (2-amino-phosphono-carboxylic acids) we found that
mitogen
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
in
cells bathed in medium containing physiological levels of bicarbonate
(10-30
mM). In addition to abolishing the mitogen-induced alkalinization,
bicarbonate stabilizes pHi at 7.25 units as the external pH (pHe) is
varied
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
external
pH, increasing the bicarbonate/CO2 concentration results in an increase
in
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
C. Our
results suggest that the observations of mitogen-induced alkalinization
may
be due to the use of nonphysiological bicarbonate-free media. Since
this
increase in pHi is not observed in physiological media where bicarbonate
concentrations are usually greater than 20 mM, we conclude that an
increase
in pHi is not an obligatory or usual part of the cellular response
to growth
factors in vivo.
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Unique Identifier
96297727
Authors
Marre D.
Institution
Institute Bergonie, Bordeaux.
Title
[Claude Lagarde]. [French]
Original Title
Le professeur Claude Lagarde.
Source
Bulletin du Cancer. 83(4):251-2, 1996 Apr.
NLM Journal Code
bdz
Journal Subset
C
Country of Publication
France
MeSH Subject Headings
Aged
France
History of Medicine, 20th Cent
Human
Male
Portraits
Radiotherapy / hi [History]
Personal Name as Subject
Lagarde C.
ISSN
0007-4551
Publication Type
Biography. Historical Article. Journal Article.
Language
French
Entry Month
199610