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Lookup NU author(s): Dr Michael Gray
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ElevatedCO(2) 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 cAMPlevels 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.
Author(s): Cook ZC, Gray MA, Cann MJ
Publication type: Article
Publication status: Published
Journal: Journal of Biological Chemistry
Print publication date: 27/07/2012
ISSN (print): 0021-9258
ISSN (electronic): 1067-8816
Publisher: American Society for Biochemistry and Molecular Biology, Inc.
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