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Rapid refilling of Ca2+ stores in macrophages stimulated by ATP involves the sequential activation of phospholipase D and protein kinase C

Abstract

Ca2+ movements between intracellular stores, the cytoplasm and external solution were analysed in murine peritoneal macrophages stimulated by various agonists. The Ca2+ content of intracellular stores was estimated from the amplitude of Ca2+-transients elicited by ionomycin applied in Ca2+-free solution. Both uridine 5′-triphosphate (UTP) and platelet-activating factor (PAF) triggered the release of Ca2+ followed by a sustained influx, during which intracellular stores remained totally empty. In contrast, in the continuous presence of adenosine 5′-triphosphate (ATP), Ca2+ was initially released and then rapidly sequestered again by the stores. ATP-induced store refilling was not related to cell depolarization or to an increase in the intracellular Na+ concentration (two specific consequences of ATP stimulation which are not induced by PAF and UTP). Store refilling was not caused by a signal that ATP would fail to induce (e.g. as a result of receptor desensitization), but was positively controlled by ATP, even in the simultaneous presence of a concentration of PAF which, on its own, would have caused a persistent store depletion. The hypothesis that the signal delivered by ATP involves the sequential activation of phospholipase D and protein kinase C is consistent with the present pharmacological evidence. However, although we found conditions in which Ca2+ stores did not refill in the presence of ATP, this maintained store depletion was not accompanied by a sustained Ca2+ response similar to that elicited by PAF or UTP, suggesting that store depletion is a condition which is necessary, but not sufficient, for inducing Ca2+ influx.

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Correspondence to Alain Trautmann.

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Alonso-Torre, S.R., Trautmann, A. Rapid refilling of Ca2+ stores in macrophages stimulated by ATP involves the sequential activation of phospholipase D and protein kinase C. Pflügers Arch. 430, 230–237 (1995). https://doi.org/10.1007/BF00374654

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Key words

  • Calcium stores
  • Platelet-activating factor
  • Uridine 5′-triphosphate
  • Adenosine 5′-triphosphate
  • Macrophages
  • Fura-2