Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
41
|
| pubmed:dateCreated |
1994-11-17
|
| pubmed:abstractText |
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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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Calcimycin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Carbachol,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glucagon,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucagon,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
14
|
| pubmed:volume |
269
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
25400-5
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:7929237-Adenylate Cyclase,
pubmed-meshheading:7929237-Adrenergic beta-Agonists,
pubmed-meshheading:7929237-Calcimycin,
pubmed-meshheading:7929237-Calcium,
pubmed-meshheading:7929237-Calmodulin,
pubmed-meshheading:7929237-Carbachol,
pubmed-meshheading:7929237-Cells, Cultured,
pubmed-meshheading:7929237-Dose-Response Relationship, Drug,
pubmed-meshheading:7929237-Drug Synergism,
pubmed-meshheading:7929237-Enzyme Activation,
pubmed-meshheading:7929237-GTP-Binding Proteins,
pubmed-meshheading:7929237-Glucagon,
pubmed-meshheading:7929237-Humans,
pubmed-meshheading:7929237-Isoproterenol,
pubmed-meshheading:7929237-Kidney,
pubmed-meshheading:7929237-Protein Kinase Inhibitors,
pubmed-meshheading:7929237-Receptors, Adrenergic, beta,
pubmed-meshheading:7929237-Receptors, Cell Surface,
pubmed-meshheading:7929237-Receptors, Glucagon,
pubmed-meshheading:7929237-Recombinant Proteins
|
| pubmed:year |
1994
|
| pubmed:articleTitle |
Synergistic activation of the type I adenylyl cyclase by Ca2+ and Gs-coupled receptors in vivo.
|
| pubmed:affiliation |
Department of Pharmacology, University of Washington, Washington 98195.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|