Elevated Carbon Dioxide Blunts Mammalian cAMP Signaling Dependent on Inositol 1,4,5-Triphosphate Receptor-mediated Ca2+ Release

Cook, Z.C.; Gray, M.A.; Cann, M.J.

doi:10.1074/jbc.m112.349191

Elevated Carbon Dioxide Blunts Mammalian cAMP Signaling Dependent on Inositol 1,4,5-Triphosphate Receptor-mediated Ca2+ Release

Cook, Z.C.; Gray, M.A.; Cann, M.J.

Authors

Z.C. Cook

M.A. Gray

Professor Martin Cann m.j.cann@durham.ac.uk
Professor

Abstract

Elevated CO2 is generally detrimental to animal cells, suggesting an interaction with core processes in cell biology. We demonstrate that elevated CO2 blunts G protein-activated cAMP signaling. The effect of CO2 is independent of changes in intracellular and extracellular pH, independent of the mechanism used to activate the cAMP signaling pathway, and is independent of cell context. A combination of pharmacological and genetic tools demonstrated that the effect of elevated CO2 on cAMP levels required the activity of the IP3 receptor. Consistent with these findings, CO2 caused an increase in steady state cytoplasmic Ca2+ concentrations not observed in the absence of the IP3 receptor or under nonspecific acidotic conditions. We examined the well characterized cAMP-dependent inhibition of the isoform 3 Na+/H+ antiporter (NHE3) to demonstrate a functional relevance for CO2-mediated reductions in cellular cAMP. Consistent with the cellular biochemistry, elevated CO2 abrogated the inhibitory effect of cAMP on NHE3 function via an IP3 receptor-dependent mechanism.

Citation

Cook, Z., Gray, M., & Cann, M. (2012). Elevated Carbon Dioxide Blunts Mammalian cAMP Signaling Dependent on Inositol 1,4,5-Triphosphate Receptor-mediated Ca2+ Release. Journal of Biological Chemistry, 287(31), 26291-26301. https://doi.org/10.1074/jbc.m112.349191

Journal Article Type	Article
Publication Date	Jul 27, 2012
Deposit Date	Aug 13, 2012
Publicly Available Date	Mar 2, 2015
Journal	Journal of Biological Chemistry
Print ISSN	0021-9258
Electronic ISSN	1083-351X
Publisher	American Society for Biochemistry and Molecular Biology
Peer Reviewed	Peer Reviewed
Volume	287
Issue	31
Pages	26291-26301
DOI	https://doi.org/10.1074/jbc.m112.349191
Keywords	Adenylate cyclase (Adenylyl cyclase), Carbon dioxide, Cyclic AMP (cAMP), Inositol 1,4,5-trisphosphate, Parathyroid hormone.

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© 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License applies to Author Choice Articles.