%0 Journal Article %1 Rochais2007 %A Rochais, F. %A Vilardaga, J. P. %A Nikolaev, V. O. %A Bunemann, M. %A Lohse, M. J. %A Engelhardt, S. %D 2007 %J J Clin Invest %K *Arginine *Genetic Acid Adrenergic Amino Base Carbazoles/*pharmacology Cell Energy Fluorescence Line Propanolamines/*pharmacology Proteins/drug Recombinant Resonance Sequence Substitution Transfection Transfer Variation beta-1/drug beta-Antagonists/*pharmacology effects/*genetics/*physiology effects/metabolism Receptor %N 1 %P 229-35 %T Real-time optical recording of beta1-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17200720 %V 117 %X Antagonists of beta-adrenergic receptors (beta-ARs) have become a main therapeutic regimen for the treatment of heart failure even though the mechanisms of their beneficial effects are still poorly understood. Here, we used fluorescent resonance energy transfer-based (FRET-based) approaches to directly monitor activation of the beta(1)-AR and downstream signaling. While the commonly used beta-AR antagonists metoprolol, bisoprolol, and carvedilol displayed varying degrees of inverse agonism on the Gly389 variant of the receptor (i.e., actively switching off the beta(1)-AR), surprisingly, only carvedilol showed very specific and marked inverse agonist effects on the more frequent Arg389 variant. These specific effects of carvedilol on the Arg389 variant of the beta(1)-AR were also seen for control of beating frequency in rat cardiac myocytes expressing the 2 receptor variants. This FRET sensor permitted direct observation of activation of the beta(1)-AR in living cells in real time. It revealed that beta(1)-AR variants dramatically differ in their responses to diverse beta blockers, with possible consequences for their clinical use.

@article{Rochais2007, abstract = {Antagonists of beta-adrenergic receptors (beta-ARs) have become a main therapeutic regimen for the treatment of heart failure even though the mechanisms of their beneficial effects are still poorly understood. Here, we used fluorescent resonance energy transfer-based (FRET-based) approaches to directly monitor activation of the beta(1)-AR and downstream signaling. While the commonly used beta-AR antagonists metoprolol, bisoprolol, and carvedilol displayed varying degrees of inverse agonism on the Gly389 variant of the receptor (i.e., actively switching off the beta(1)-AR), surprisingly, only carvedilol showed very specific and marked inverse agonist effects on the more frequent Arg389 variant. These specific effects of carvedilol on the Arg389 variant of the beta(1)-AR were also seen for control of beating frequency in rat cardiac myocytes expressing the 2 receptor variants. This FRET sensor permitted direct observation of activation of the beta(1)-AR in living cells in real time. It revealed that beta(1)-AR variants dramatically differ in their responses to diverse beta blockers, with possible consequences for their clinical use.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Rochais, F. and Vilardaga, J. P. and Nikolaev, V. O. and Bunemann, M. and Lohse, M. J. and Engelhardt, S.}, biburl = {https://www.bibsonomy.org/bibtex/29e192eb98de7a98f2c4088f58192f4b0/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {a54e5e0f3fa0e63579646201bc10f325}, intrahash = {9e192eb98de7a98f2c4088f58192f4b0}, issn = {0021-9738 (Print) 0021-9738 (Linking)}, journal = {J Clin Invest}, keywords = {*Arginine *Genetic Acid Adrenergic Amino Base Carbazoles/*pharmacology Cell Energy Fluorescence Line Propanolamines/*pharmacology Proteins/drug Recombinant Resonance Sequence Substitution Transfection Transfer Variation beta-1/drug beta-Antagonists/*pharmacology effects/*genetics/*physiology effects/metabolism Receptor}, month = Jan, note = {Rochais, Francesca Vilardaga, Jean-Pierre Nikolaev, Viacheslav O Bunemann, Moritz Lohse, Martin J Engelhardt, Stefan Research Support, Non-U.S. Gov't United States The Journal of clinical investigation J Clin Invest. 2007 Jan;117(1):229-35.}, number = 1, pages = {229-35}, shorttitle = {Real-time optical recording of beta1-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol}, timestamp = {2010-12-14T18:22:42.000+0100}, title = {Real-time optical recording of beta1-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17200720}, volume = 117, year = 2007 }