Publication details for Professor Martin CannCook, Z.C., Gray, M.A. & Cann, M.J. (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.
- Publication type: Journal Article
- ISSN/ISBN: 0021-9258 (print), 1083-351X (electronic)
- DOI: 10.1074/jbc.M112.349191
- Keywords: Adenylate cyclase (Adenylyl cyclase), Carbon dioxide, Cyclic AMP (cAMP), Inositol 1,4,5-trisphosphate, Parathyroid hormone.
- Further publication details on publisher web site
- Durham Research Online (DRO) - may include full text
Author(s) from Durham
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.