Autor: |
Cook ZC; School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, United Kingdom., Gray MA, Cann MJ |
Jazyk: |
angličtina |
Zdroj: |
The Journal of biological chemistry [J Biol Chem] 2012 Jul 27; Vol. 287 (31), pp. 26291-301. Date of Electronic Publication: 2012 May 31. |
DOI: |
10.1074/jbc.M112.349191 |
Abstrakt: |
Elevated CO(2) is generally detrimental to animal cells, suggesting an interaction with core processes in cell biology. We demonstrate that elevated CO(2) blunts G protein-activated cAMP signaling. The effect of CO(2) 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 CO(2) on cAMP levels required the activity of the IP(3) receptor. Consistent with these findings, CO(2) caused an increase in steady state cytoplasmic Ca(2+) concentrations not observed in the absence of the IP(3) 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 CO(2)-mediated reductions in cellular cAMP. Consistent with the cellular biochemistry, elevated CO(2) abrogated the inhibitory effect of cAMP on NHE3 function via an IP(3) receptor-dependent mechanism. |
Databáze: |
MEDLINE |
Externí odkaz: |
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