Journal article
Synergistic activation of the type I adenylyl cyclase by Ca2+ and Gs-coupled receptors in vivo
The Journal of biological chemistry, Vol.269(41), pp.25400-25405
10/14/1994
Handle:
https://hdl.handle.net/2376/112787
PMID: 7929237
Abstract
The type I adenylyl cyclase is directly stimulated by Ca2+ and calmodulin in vivo (Choi, E. J., Wong, S. T., Hinds, T. R. and Storm, D. R. (1992) J. Biol. Chem. 267, 12440-12442; Wu, Z., Wong, S. T., and Storm, D. R. (1993) J. Biol. Chem. 268, 23766-23768). In this study, we examined the sensitivity of the type I adenylyl cyclase expressed in HEK-293 cells to beta-adrenergic agonists or glucagon when intracellular Ca2+ was elevated by Ca2+ ionophore or carbachol. Although previous studies have shown that this enzyme can be directly stimulated by activated Gs in vitro, we demonstrate that it is not stimulated by Gs-coupled receptors in vivo. However, the enzyme was stimulated by Gs-coupled receptors in vivo when it was activated by intracellular Ca2+. For example, the Ca2+ ionophore A23187 stimulated the enzyme 3 +/- 0.5-fold (n = 9) and isoproterenol alone did not stimulate the enzyme, but the combination of the two stimulated type I adenylyl cyclase 13 +/- 2-fold (n = 9) in vivo. Similarly, 500 nM glucagon alone did not stimulate the enzyme but the combination of A23187 and glucagon activated the enzyme 90 +/- 8-fold (n = 4). Synergistic stimulation of type I adenylyl cyclase activity was also obtained with combinations of carbachol and isoproterenol or glucagon. This phenomenon was not observed with a mutant enzyme that is insensitive to Ca2+ and calmodulin, suggesting that conformational changes caused by binding of calmodulin to the type I adenylyl cyclase enhance binding or coupling to activated Gs. These data illustrate that this adenylyl cyclase can couple Ca2+ and neurotransmitter signals to generate optimal cAMP levels, a property of the enzyme that may be important for its role in learning and memory in mammals.
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Details
- Title
- Synergistic activation of the type I adenylyl cyclase by Ca2+ and Gs-coupled receptors in vivo
- Creators
- G A Wayman - Department of Pharmacology, University of Washington, Washington 98195S ImpeyZ WuW KindsvogelL PrichardD R Storm
- Publication Details
- The Journal of biological chemistry, Vol.269(41), pp.25400-25405
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- United States
- Grant note
- NS 20498 / NINDS NIH HHS
- Identifiers
- 99900547686101842
- Language
- English
- Resource Type
- Journal article