Feedback regulation of ATP-induced Ca2+ signaling in HL-60 cells is mediated by protein kinase A- and C-mediated changes in capacitative Ca2+ entry

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Extracellular ATP increases intracellular Ca2+ ([Ca2+](i)) in HL-60 cells. When cells are stimulated with supramaximal concentrations of ATP, although the initial [Ca2+](i) increase is similar over a range of 30, 100, and 300 μM ATP, the rate of the return to basal [Ca2+](i) level is faster in cells treated with higher concentrations of ATP. This probably results from differences in Ca2+ influx rather than Ca2+ release, since the influx of the unidirectional Ca2+ surrogates Ba2+ and Mn2+ also exhibit similar responses. Furthermore, while 300 μM ATP had an inhibitory effect on the thapsigargin-induced capacitative Ca2+ entry, 30 μM ATP potentiated the response. However, the inhibitory action of 300 μM ATP was blocked by protein kinase C (PKC) inhibitors, such as GF 109203X and chelerythrine, and the potentiating action of 30 μM ATP was blocked by protein kinase A (PKA) inhibitors H89 and Rp-cAMPS. The PKC inhibitors also slowed the decay rate of the Ca2+ response induced by 300 μM ATP, and the PKA inhibitors increased it when induced by 30 μM ATP. In the measurements of PKA and PKC activity, 30 μM ATP activates only PKA, while 300 μM ATP activates both kinases. Taken together, these data suggest that the changes in the ATP-induced Ca2+ response result from differential modulation of ATP-induced capacitative Ca2+ entry by PKC and PKA in HL-60 cells.

Original languageEnglish
Pages (from-to)21831-21838
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number35
DOIs
StatePublished - 29 Aug 1997

Fingerprint

Dive into the research topics of 'Feedback regulation of ATP-induced Ca2+ signaling in HL-60 cells is mediated by protein kinase A- and C-mediated changes in capacitative Ca2+ entry'. Together they form a unique fingerprint.

Cite this