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dc.contributor.author
Pleli, Thomas
dc.contributor.author
Mondorf, Antonia
dc.contributor.author
Ferreiros, Nerea
dc.contributor.author
Thomas, Dominique
dc.contributor.author
Dvorak, Karel
dc.contributor.author
Biondi, Ricardo Miguel
dc.contributor.author
Heringdorf, Dagmar Meyer zu
dc.contributor.author
Zeuzem, Stefan
dc.contributor.author
Geisslinger, Gerd
dc.contributor.author
Zimmermann, Herbert
dc.contributor.author
Waidmann, Oliver
dc.contributor.author
Piiper, Albrecht
dc.date.available
2019-11-07T19:49:35Z
dc.date.issued
2018-05
dc.identifier.citation
Pleli, Thomas; Mondorf, Antonia; Ferreiros, Nerea; Thomas, Dominique; Dvorak, Karel; et al.; Activation of Adenylyl Cyclase Causes Stimulation of Adenosine Receptors; Karger; Cellular Physiology and Biochemistry; 45; 6; 5-2018; 2516-2528
dc.identifier.issn
1015-8987
dc.identifier.uri
http://hdl.handle.net/11336/88238
dc.description.abstract
AbstractBACKGROUND/AIMS:Signaling of Gs protein-coupled receptors (GsPCRs) is accomplished by stimulation of adenylyl cyclase, causing an increase of the intracellular cAMP concentration, activation of the intracellular cAMP effectors protein kinase A (PKA) and Epac, and an efflux of cAMP, the function of which is still unclear.METHODS:Activation of adenylyl cyclase by GsPCR agonists or cholera toxin was monitored by measurement of the intracellular cAMP concentration by ELISA, anti-phospho-PKA substrate motif phosphorylation by immunoblotting, and an Epac-FRET assay in the presence and absence of adenosine receptor antagonists or ecto-nucleotide phosphodiesterase/pyrophosphatase2 (eNPP2) inhibitors. The production of AMP from cAMP by recombinant eNPP2 was measured by HPLC. Extracellular adenosine was determined by LC-MS/MS, extracellular ATP by luciferase and LC-MS/MS. The expression of eNPP isoenzymes 1-3 was examined by RT-PCR. The expression of multidrug resistance protein 4 was suppressed by siRNA.RESULTS:Here we show that the activation of GsPCRs and the GsPCRs-independent activation of Gs proteins and adenylyl cyclase by cholera toxin induce stimulation of cell surface adenosine receptors (A2A or A2B adenosine receptors). In PC12 cells stimulation of adenylyl cyclase by GsPCR or cholera toxin caused activation of A2A adenosine receptors by an autocrine signaling pathway involving cAMP efflux through multidrug resistance protein 4 and hydrolysis of released cAMP to AMP by eNPP2. In contrast, in PC3 cells cholera toxin- and GsPCR-induced stimulation of adenylyl cyclase resulted in the activation of A2B adenosine receptors.CONCLUSION:Our findings show that stimulation of adenylyl cyclase causes a remarkable activation of cell surface adenosine receptors.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Karger
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Adenosine
dc.subject
Adenylyl Cyclase
dc.subject
cAMP
dc.subject
autocrine
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Activation of Adenylyl Cyclase Causes Stimulation of Adenosine Receptors
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-22T17:54:08Z
dc.journal.volume
45
dc.journal.number
6
dc.journal.pagination
2516-2528
dc.journal.pais
Suiza
dc.description.fil
Fil: Pleli, Thomas. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Mondorf, Antonia. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Ferreiros, Nerea. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Thomas, Dominique. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Dvorak, Karel. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Biondi, Ricardo Miguel. Goethe Universitat Frankfurt; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
dc.description.fil
Fil: Heringdorf, Dagmar Meyer zu. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Zeuzem, Stefan. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Geisslinger, Gerd. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Zimmermann, Herbert. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Waidmann, Oliver. Goethe Universitat Frankfurt; Alemania
dc.description.fil
Fil: Piiper, Albrecht. Goethe Universitat Frankfurt; Alemania
dc.journal.title
Cellular Physiology and Biochemistry
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/FullText/488270
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1159/000488270
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