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Interrelationship between growth factor-induced pH changes and intracellular Ca2+.

H E Ives, T O Daniel

    Proceedings of the National Academy of Sciences of the United States of America
    |April 1, 1987
    PubMed
    Summary
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    Platelet-derived growth factor (PDGF) and other mitogens alter fibroblast pH and calcium (Ca2+). Acidification is Ca2+-dependent, while subsequent alkalinization via the Na+/H+ exchanger is Ca2+-independent.

    Area of Science:

    • Cell biology
    • Biochemistry
    • Physiology

    Background:

    • Mitogens rapidly alter intracellular pH and Ca2+ levels in cells.
    • Understanding these signaling pathways is crucial for cell growth and function.

    Purpose of the Study:

    • To investigate the distinct patterns of intracellular pH and Ca2+ changes induced by various mitogens in murine fibroblasts.
    • To elucidate the relationship between Ca2+ fluxes and pH alterations.

    Main Methods:

    • Murine fibroblasts were exposed to platelet-derived growth factor (PDGF), bombesin, phorbol 12-myristate 13-acetate (PMA), and bradykinin.
    • Intracellular pH and Ca2+ were measured using fluorescent dyes (2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein and fura-2).
    • Ca2+ buffering with quin-2 was employed to assess the role of Ca2+ in pH changes.

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    Main Results:

    • Three distinct intracellular pH patterns were observed: rapid acidification followed by alkalinization (PDGF, bombesin), alkalinization without early acidification (PMA), and rapid acidification without net alkalinization (bradykinin, ionomycin).
    • PDGF and bombesin induced transient increases in intracellular Ca2+, while PMA did not, and bradykinin caused the most rapid Ca2+ increase.
    • Cellular acidification responses were amiloride-resistant and Ca2+-dependent, whereas alkalinization responses persisted even when Ca2+ was buffered.

    Conclusions:

    • Transient cellular acidification induced by mitogens like PDGF is primarily mediated by increased intracellular Ca2+.
    • Growth factor-induced alkalinization, occurring via the Na+/H+ exchanger, is independent of Ca2+ signaling.
    • These findings differentiate the signaling mechanisms underlying pH and Ca2+ dynamics in response to mitogenic stimuli.