Inhibition of inositol 1,4,5-trisphosphate-induced Ca2+ release by cAMP-dependent protein kinase in a living cell
AUTOR(ES)
Tertyshnikova, Svetlana
FONTE
The National Academy of Sciences
RESUMO
Interaction of intracellular free calcium ([Ca2+]i) and cAMP signaling mechanisms was examined in intact single megakaryocytes by using a combination of single-cell fluorescence microscopy to measure [Ca2+]i and flash photolysis of caged Ca2+, inositol 1,4,5-trisphosphate (IP3), or cAMP to elevate rapidly the concentration of these compounds inside the cell. Photolysis of caged IP3 stimulated Ca2+ release from an IP3-sensitive store. The cAMP-elevating agent carbacyclin inhibited this IP3-induced rise in [Ca2+]i but did not affect the rate of Ca2+ removal from the cytoplasm after photolysis of caged Ca2+. Photolysis of caged cAMP during ADP-induced [Ca2+]i oscillations caused the [Ca2+]i oscillation to transiently cease without affecting the rate of Ca2+ uptake and/or extrusion. We conclude that the principal mechanism of cAMP-dependent inhibition of Ca2+ mobilization in megakaryocytes appears to be by inhibition of IP3-induced Ca2+ release and not by stimulation of Ca2+ removal from the cytoplasm. Two inhibitors of cAMP-dependent protein kinase, a specific peptide inhibitor of the catalytic subunit of cAMP protein kinase and KT5720, blocked the inhibitory effect of carbacyclin, indicating that the inhibition of IP3-induced Ca2+-release by carbacyclin is mediated by cAMP-dependent protein kinase.
ACESSO AO ARTIGO
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