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Interrelationship between growth factor-induced pH changes and intracellular Ca/sup 2 +/

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
Many mitogens cause rapid changes in intracellular pH and Ca/sup 2 +/. The authors studied the patterns of pH and Ca/sup 2 +/ changes after exposure of murine fibroblasts to platelet-derived growth factor (PDGF), bombesin, phorbol 12-myristate 13-acetate (PMA), and the vasoactive peptide bradykinin. Intracellular pH and Ca/sup 2 +/ were measured by using the fluorescent dyes 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein and fura-2. Three distinct patterns of intracellular pH change were observed. (i) PDGF and bombesin caused a rapid cytoplasmic acidification of 0.03 pH unit followed by a slower alkalinization of approx. = 0.11 pH unit above the resting pH of 6.88. (ii) PMA caused alkalinization without causing the early acidification. (iii) Bradykinin caused rapid acidification without the slower net alkalinization. All acidification responses were amiloride resistant. Patterns of intracellular Ca/sup 2 +/ response were also determined for each agent. In Ca/sup 2 +/-buffered cells, PDGF, bombesin, bradykinin, and ionomycin failed to induce cellular acidification, but alkalinization responses to PDGF, bombesin, and PMA persisted. They propose that the transient acidification seen with PDGF, bombesin, and other agents is the result of increased intracellular Ca/sup 2 +/. However, growth factor-induced alkalinization via the Na/sup +//H/sup +/ exchanger is independent of changes in Ca/sup 2 +/.
Research Organization:
Univ. of California, San Francisco
OSTI ID:
5897379
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:7; ISSN PNASA
Country of Publication:
United States
Language:
English