The relative contributions of extracellular and intracellular calcium to secretion from tumor mast cells. Mutiple effects of the proton ionophore carbonyl cyanide m-chlorophenylhydrazone

Frederick C Mohr, C. Fewtrell

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited antigen-stimulated secretion and calcium influx in rat basophilic leukemia cells. In a glucose-free solution the inhibitory effects of CCCP were due to a decrease in the intracellular ATP concentration; however, when glucose was present there was no decrease in ATP. Instead, we found that in a glucose-containing saline solution, CCCP inhibited antigen-stimulated calcium uptake because it depolarized the plasma membrane, which in rat basophilic leukemia cells inhibits antigen-stimulated calcium uptake. In the presence of glucose, relatively low concentrations of CCCP inhibited calcium uptake while higher concentrations were required to inhibit secretion. In contrast, the initial antigen-stimulated rise in cytoplasmic calcium, measured with the fluorescent calcium indicator quin2, was not inhibited by CCCP. This suggests that the release of calcium from intracellular stores might, in some cases, be sufficient to support antigen-stimulated secretion. In the presence of CCCP the pH gradient becomes important for regulating the membrane potential across the plasma membrane. When cells were depolarized with CCCP and the external pH was increased, the membrane potential returned to resting levels and antigen-stimulated calcium uptake was restored. Inhibition of antigen-stimulated secretion by higher concentrations of CCCP could also be reversed by increasing the external pH.

Original languageEnglish (US)
Pages (from-to)10638-10643
Number of pages6
JournalJournal of Biological Chemistry
Volume262
Issue number22
StatePublished - 1987
Externally publishedYes

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Proton Ionophores
Mast Cells
Tumors
Calcium
Antigens
Neoplasms
Glucose
Cell membranes
Membrane Potentials
Rats
Leukemia
Adenosine Triphosphate
Cell Membrane
Membranes
Proton-Motive Force
mesoxalonitrile
carbonyl 3-chlorophenylhydrazone
Sodium Chloride

ASJC Scopus subject areas

  • Biochemistry

Cite this

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abstract = "The proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited antigen-stimulated secretion and calcium influx in rat basophilic leukemia cells. In a glucose-free solution the inhibitory effects of CCCP were due to a decrease in the intracellular ATP concentration; however, when glucose was present there was no decrease in ATP. Instead, we found that in a glucose-containing saline solution, CCCP inhibited antigen-stimulated calcium uptake because it depolarized the plasma membrane, which in rat basophilic leukemia cells inhibits antigen-stimulated calcium uptake. In the presence of glucose, relatively low concentrations of CCCP inhibited calcium uptake while higher concentrations were required to inhibit secretion. In contrast, the initial antigen-stimulated rise in cytoplasmic calcium, measured with the fluorescent calcium indicator quin2, was not inhibited by CCCP. This suggests that the release of calcium from intracellular stores might, in some cases, be sufficient to support antigen-stimulated secretion. In the presence of CCCP the pH gradient becomes important for regulating the membrane potential across the plasma membrane. When cells were depolarized with CCCP and the external pH was increased, the membrane potential returned to resting levels and antigen-stimulated calcium uptake was restored. Inhibition of antigen-stimulated secretion by higher concentrations of CCCP could also be reversed by increasing the external pH.",
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N2 - The proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited antigen-stimulated secretion and calcium influx in rat basophilic leukemia cells. In a glucose-free solution the inhibitory effects of CCCP were due to a decrease in the intracellular ATP concentration; however, when glucose was present there was no decrease in ATP. Instead, we found that in a glucose-containing saline solution, CCCP inhibited antigen-stimulated calcium uptake because it depolarized the plasma membrane, which in rat basophilic leukemia cells inhibits antigen-stimulated calcium uptake. In the presence of glucose, relatively low concentrations of CCCP inhibited calcium uptake while higher concentrations were required to inhibit secretion. In contrast, the initial antigen-stimulated rise in cytoplasmic calcium, measured with the fluorescent calcium indicator quin2, was not inhibited by CCCP. This suggests that the release of calcium from intracellular stores might, in some cases, be sufficient to support antigen-stimulated secretion. In the presence of CCCP the pH gradient becomes important for regulating the membrane potential across the plasma membrane. When cells were depolarized with CCCP and the external pH was increased, the membrane potential returned to resting levels and antigen-stimulated calcium uptake was restored. Inhibition of antigen-stimulated secretion by higher concentrations of CCCP could also be reversed by increasing the external pH.

AB - The proton ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited antigen-stimulated secretion and calcium influx in rat basophilic leukemia cells. In a glucose-free solution the inhibitory effects of CCCP were due to a decrease in the intracellular ATP concentration; however, when glucose was present there was no decrease in ATP. Instead, we found that in a glucose-containing saline solution, CCCP inhibited antigen-stimulated calcium uptake because it depolarized the plasma membrane, which in rat basophilic leukemia cells inhibits antigen-stimulated calcium uptake. In the presence of glucose, relatively low concentrations of CCCP inhibited calcium uptake while higher concentrations were required to inhibit secretion. In contrast, the initial antigen-stimulated rise in cytoplasmic calcium, measured with the fluorescent calcium indicator quin2, was not inhibited by CCCP. This suggests that the release of calcium from intracellular stores might, in some cases, be sufficient to support antigen-stimulated secretion. In the presence of CCCP the pH gradient becomes important for regulating the membrane potential across the plasma membrane. When cells were depolarized with CCCP and the external pH was increased, the membrane potential returned to resting levels and antigen-stimulated calcium uptake was restored. Inhibition of antigen-stimulated secretion by higher concentrations of CCCP could also be reversed by increasing the external pH.

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