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10.1038/embor.2013.4 http://scihub22266oqcxt.onion/10.1038/embor.2013.4 23381222!3589095!23381222     free     free     free       EMBO+Rep 2013 ; 14 (3): 276-83 Nephropedia Template TP {{tp|p=23381222|t=2013. beta1-adrenergic receptor antagonists signal via PDE4 translocation |pdf=|usr=}}{{23381222}} gab.com Text beta1-adrenergic receptor antagonists signal via PDE4 translocation JO: EMBO Rep http://www.kidney.de/pget.php?&tw=1&pmid=23381222 #FOAvip It is generally assumed that antagonists of Gs-coupled receptors do not activate cAMP signalling, because they do not stimulate cAMP production via Gs-protein/adenylyl cyclase activation. Here, we report a new signalling pathway whereby antagonists of beta1-adrenergic receptors (beta1ARs) increase cAMP levels locally without stimulating cAMP production directly. Binding of antagonists causes dissociation of a preformed complex between beta1ARs and Type-4 cyclic nucleotide phosphodiesterases (PDE4s). This reduces the local concentration of cAMP-hydrolytic activity, thereby increasing submembrane cAMP and PKA activity. Our study identifies receptor/PDE4 complex dissociation as a novel mechanism of antagonist action that contributes to the pharmacological properties of beta1AR antagonists and might be shared by other receptor subtypes. Twit Text FOAVip beta1-adrenergic receptor antagonists signal via PDE4 translocation ????EMBO Rep http://www.kidney.de/pget.php?&tw=1&pmid=23381222 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=23381222 #FOAvip English Wikipedia <ref>{{Cite pmid|23381222}}</ref> beta1-adrenergic receptor antagonists signal via PDE4 translocation #MMPMID23381222 Richter W; Mika D; Blanchard E; Day P; Conti M EMBO Rep 2013[Mar]; 14 (3): 276-83 PMID23381222show ga It is generally assumed that antagonists of Gs-coupled receptors do not activate cAMP signalling, because they do not stimulate cAMP production via Gs-protein/adenylyl cyclase activation. Here, we report a new signalling pathway whereby antagonists of beta1-adrenergic receptors (beta1ARs) increase cAMP levels locally without stimulating cAMP production directly. Binding of antagonists causes dissociation of a preformed complex between beta1ARs and Type-4 cyclic nucleotide phosphodiesterases (PDE4s). This reduces the local concentration of cAMP-hydrolytic activity, thereby increasing submembrane cAMP and PKA activity. Our study identifies receptor/PDE4 complex dissociation as a novel mechanism of antagonist action that contributes to the pharmacological properties of beta1AR antagonists and might be shared by other receptor subtypes. |Adrenergic beta-1 Receptor Antagonists/*pharmacology[MESH] |Cell Membrane/metabolism[MESH] |Cyclic AMP-Dependent Protein Kinases/metabolism[MESH] |Cyclic AMP/metabolism[MESH] |Cyclic Nucleotide Phosphodiesterases, Type 4/*metabolism[MESH] |HEK293 Cells[MESH] |Humans[MESH] |Protein Binding/drug effects[MESH] |Protein Transport/drug effects[MESH] |Receptors, Adrenergic, beta-1/drug effects/*metabolism[MESH]beta1-adrenergic receptor antagonists signal via PDE4 translocation (epmc).pdf DeepDyve Pubget Overpricing