Calcium and muscarinic agonist stimulation of type I adenylylcyclase in whole cells.
Open accessAbstract
The type I adenylylcyclase which was originally purified and cloned from bovine brain is stimulated by Ca2+ and calmodulin in vitro. Although it has been proposed that this enzyme may couple elevations in intracellular Ca2+ to increases in cAMP in whole cells, this has not been demonstrated in vivo. In this study, the type I adenylylcyclase was expressed in human 293 cells, and the influence of extracellular Ca2+ and Ca2+ ionophore on intracellular cAMP levels was examined. The cAMP levels of control cells were unaffected by Ca2+ and A23187. In contrast, intracellular cAMP in 293 cells expressing type I adenylylcyclase was markedly elevated by addition of A23187 and extracellular Ca2+. In the presence of forskolin, the muscarinic agonist carbachol also increased cAMP in 293 cells expressing the type I adenylylcyclase. These data indicate that the type I adenylylcyclase can be stimulated by Ca2+ in vivo, and that muscarinic agonists may indirectly stimulate the enzyme by increasing intracellular free Ca2+.
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AC1 is stimulated directly by Ca2+ and CaM in vivo, with halfmaximal stimulation at 200 nM free Ca2+.
“AC1 is stimulated directly by Ca 2ϩ and CaM in vivo (Choi et al., 1992;Wu et al., 1993), with halfmaximal stimulation at 200 nM free C a 2ϩ .”
From Type I Adenylyl Cyclase Mutant Mice Have Impaired Mossy Fiber Long-Term Potentiation (1998) · cites this paper as Choi et al., 1992
AC1 is stimulated by free Ca2+ as low as 150-200 nM.
“It is stimulated by free Ca 2ϩ as low as 150 -200 nM (Choi et al., 1992;Villacres et al., 1995)”
From Type I Adenylyl Cyclase Mutant Mice Have Impaired Mossy Fiber Long-Term Potentiation (1998) · cites this paper as Choi et al., 1992
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Wu, Z. L., Thomas, S. A., Villacres, E. C., Xia, Z., Simmons, M. L., Chavkin, C., Palmiter, R. D., & Storm, D. R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.1.220 · Cited by 370 · see citing works
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Villacres, E. C., Wong, S. T., Chavkin, C., & Storm, D. R. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-09-03186.1998 · Cited by 187 · see citing works
“AC1 is stimulated directly by Ca 21 and CaM in vivo (Choi et al., 1992; Wu et al., 1993), with halfmaximal stimulation at 200 nM free Ca21.”
BackgroundSelf-citationSynergistic activation of the type I adenylyl cyclase by Ca2+ and Gs-coupled receptors in vivo.
Wayman, G. A., Impey, S., Wu, Z., Kindsvogel, W., Prichard, L., & Storm, D. R. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47263-8 · Cited by 166 · see citing works
Self-citationImpaired Cerebellar Long-Term Potentiation in Type I Adenylyl Cyclase Mutant Mice
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Self-citationChen, X., Cao, H., Saraf, A., Zweifel, L. S., & Storm, D. R. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2478-14.2015 · Cited by 21 · see citing works
Self-citation
- Authors
- Choi, E. J., Wong, S. T., Hinds, T. R., & Storm, D. R.
- Affiliations
- University of Washington (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1992-06
- Volume
- 267
- Issue
- 18
- Pages
- 12440-12442
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1629605343
- Cited by
- 138
- References
- 0
- Citations by year
- 2021: 1 · 2015: 2 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 8.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS020498, NS20498)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
- Keywords
- calcium signaling, muscarinic agonists, carbachol, cyclic AMP, calmodulin, A23187, intracellular calcium, forskolin, 293 cells, enzyme expression
- MeSH terms
- Calcimycin, Cyclic AMP, Adenylyl Cyclases, Calcium, Carbachol, Cell Line, Enzyme Activation, Humans, Receptors, Muscarinic
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