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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2010-1-25
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pubmed:abstractText |
cAMP and Ca(2+) are antagonistic intracellular messengers for the regulation of vascular smooth muscle tone; rising levels of Ca(2+) lead to vasoconstriction, whereas an increase of cAMP induces vasodilatation. Here we investigated whether Ca(2+) interferes with cAMP signaling by regulation of phophodiesterases (PDEs) or adenylyl cyclases (ACs). We studied regulation of cAMP concentrations by Ca(2+) signals evoked by endogenous purinergic receptors in vascular smooth muscle cells (VSMCs). The fluorescence resonance energy transfer (FRET)-based cAMP sensor Epac1-camps allowed the measurement of cAMP levels in single-living VSMCs with subsecond temporal resolution. Moreover, in vitro calibration of Epac1-camps enabled us to estimate the absolute cytosolic cAMP concentrations. Stimulation of purinergic receptors decreased cAMP levels in the presence of the beta-adrenergic agonist isoproterenol. Simultaneous imaging of cAMP with Epac1-camps and of Ca(2+) with Fura 2 revealed a rise of intracellular Ca(2+) in response to purinergic stimulation followed by a decline of cAMP. Chelation of intracellular Ca(2+) and overexpression of Ca(2+)-independent AC4 antagonized this decline of cAMP, whereas pharmacological inhibition of Ca(2+)-activated PDE1 had no effect. AC assays with VSMC membranes revealed a significant attenuation of isoproterenol-stimulated cAMP production by the presence of 2 muM Ca(2+). Furthermore, small interfering RNA (siRNA) knockdown of AC5 and AC6 (the two ACs known to be inhibited by Ca(2+)), significantly reduced the decrease of cAMP upon purinergic stimulation of isoproterenol-prestimulated VSMCs. Taken together, these results implicate a Ca(2+)-mediated inhibition of AC5 and 6 as an important mechanism of purinergic receptor-induced decline of cAMP and show a direct cross talk of these signaling pathways in VSMCs.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/8-methoxymethyl-3-isobutyl-1-methylx...,
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic Nucleotide...,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic,
http://linkedlifedata.com/resource/pubmed/chemical/Uridine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Xanthines,
http://linkedlifedata.com/resource/pubmed/chemical/adenylyl cyclase 4,
http://linkedlifedata.com/resource/pubmed/chemical/adenylyl cyclase 6,
http://linkedlifedata.com/resource/pubmed/chemical/adenylyl cyclase type V
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1522-1563
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
298
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C324-32
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pubmed:dateRevised |
2010-10-13
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pubmed:meshHeading |
pubmed-meshheading:19889965-Adenylate Cyclase,
pubmed-meshheading:19889965-Adrenergic beta-Agonists,
pubmed-meshheading:19889965-Animals,
pubmed-meshheading:19889965-Aorta,
pubmed-meshheading:19889965-Biosensing Techniques,
pubmed-meshheading:19889965-Calcium Signaling,
pubmed-meshheading:19889965-Cells, Cultured,
pubmed-meshheading:19889965-Cyclic AMP,
pubmed-meshheading:19889965-Cyclic Nucleotide Phosphodiesterases, Type 1,
pubmed-meshheading:19889965-Dose-Response Relationship, Drug,
pubmed-meshheading:19889965-Fluorescence Resonance Energy Transfer,
pubmed-meshheading:19889965-GTP-Binding Protein alpha Subunits, Gq-G11,
pubmed-meshheading:19889965-Humans,
pubmed-meshheading:19889965-Isoenzymes,
pubmed-meshheading:19889965-Isoproterenol,
pubmed-meshheading:19889965-Mice,
pubmed-meshheading:19889965-Muscle, Smooth, Vascular,
pubmed-meshheading:19889965-Myocytes, Smooth Muscle,
pubmed-meshheading:19889965-Phosphodiesterase Inhibitors,
pubmed-meshheading:19889965-RNA Interference,
pubmed-meshheading:19889965-Receptors, Purinergic,
pubmed-meshheading:19889965-Time Factors,
pubmed-meshheading:19889965-Transfection,
pubmed-meshheading:19889965-Uridine Triphosphate,
pubmed-meshheading:19889965-Vasoconstriction,
pubmed-meshheading:19889965-Vasodilation,
pubmed-meshheading:19889965-Xanthines
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pubmed:year |
2010
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pubmed:articleTitle |
Gq-mediated Ca2+ signals inhibit adenylyl cyclases 5/6 in vascular smooth muscle cells.
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pubmed:affiliation |
University of Marburg, Institute of Pharmacology and Toxicology, Karl-von-Frisch-Strasse 1, 35033 Marburg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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