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J. Biol. Chem., Vol. 262, Issue 11, 5065-5072, 04, 1987
BC Berk, TA Brock, MA Gimbrone Jr and RW Alexander
Angiotensin II, a potent vasoconstrictor peptide, increases free
cytoplasmic Ca2+ concentration ([Ca2+]i) in vascular smooth muscle cells
(VSMC) by release of nonmitochondrial Ca2+ stores and stimulates an
amiloride-sensitive Na+ influx, presumably via Na+/H+ exchange. We recently
have found that the angiotensin II-mediated change in VSMC intracellular pH
has two components, an early rapid acidification phase and a slower
recovery phase involving Na+-dependent alkalinization. In the present
study, we show that the early acidification is not mediated via Na+/H+
exchange. Instead, we propose a mechanism which involves increases in
[Ca2+]i and Ca2+ efflux with a subsequent rise in intracellular H+.
Agonists, in addition to angiotensin II, which increase [Ca2+]i in cultured
VSMC, including platelet-derived growth factor, vasopressin, and
bradykinin, induce an acidification, while agonists which fail to raise
[Ca2+]i do not. The time course and magnitude of agonist-stimulated 45Ca2+
efflux correlate with the acidification response. The angiotensin II
concentration-response relationship for acidification and Ca2+ mobilization
are similar. Furthermore, inhibition of changes in [Ca2+]i by treatment
with phorbol ester, cyclic GMP, or quin2 loading prevent agonist-mediated
acidification. The effects of altering extracellular [Ca2+] and [H+] on
agonist-mediated intracellular acidification and H+ efflux suggest that the
acidification is due to ATP-dependent unidirectional H+ influx, perhaps via
the plasma membrane Ca2+-ATPase, and not to a Ca2+/H+ antiport. This
agonist-mediated acidification represents a previously undescribed ionic
event in VSMC activation which may be involved in excitation-response
coupling.
Early agonist-mediated ionic events in cultured vascular smooth muscle cells. Calcium mobilization is associated with intracellular acidification [published erratum appears in J Biol Chem 1987 Jul 25;262(21):10412]
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