%0 Journal Article %1 Lohse1996b %A Lohse, M. J. %A Engelhardt, S. %A Danner, S. %A Bohm, M. %D 1996 %J Basic Res Cardiol %K Animals Arrestins/metabolism Biology Failure/*metabolism GTP-Binding Heart Humans Messenger/*metabolism Molecular Phosphorylation Phosphotransferases/metabolism Proteins/metabolism RNA, Signal Transduction/*physiology beta/genetics/*metabolism Receptor Adrenergic %P 29-34 %T Mechanisms of beta-adrenergic receptor desensitization: from molecular biology to heart failure %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8957541 %V 91 Suppl 2 %X beta-Adrenergic receptors are often studied as prototypes of the large family of G-protein-coupled receptors, which includes many other well-known members such as the muscarinic acetylcholine receptors, but also the receptors for light, taste and olfaction. These receptors are regulated by multiple mechanisms which can affect either their function or their expression to a rapidly changing environment. The most obvious changes are effected by receptor agonists, and this process is called receptor desensitization. On the functional level, the most intriguing and important mechanism of desensitization involves the phosphorylation of beta-adrenergic and homologous receptors by specific receptor kinases, termed the G-protein-coupled receptor kinases (GRKs). This phosphorylation is followed by binding of arrestins to the receptors, which causes uncoupling of receptors and G-proteins and thus results in a loss of receptor function. On the expression level, there appear to be two major pathways leading to a reduction of the receptor number: degradation of the receptors themselves, or reduced receptor synthesis brought about by reduced receptor mRNA levels. Heart failure is accompanied by a markedly reduced responsiveness of the beta-adrenergic receptor system, which in many ways resembles the phenomena seen in agonist-induced receptor desensitization. The levels of beta 1-adrenergic receptors are reduced, and this reduction is paralleled by similar decreases in the levels of the corresponding mRNA. At the same time, the activity and the mRNA levels of one of the GRK-isoforms, GRK2 (which is identical to the beta-adrenergic receptor kinase 1) are increased. These alterations may contribute to the loss of beta-adrenergic receptor responsiveness in heart failure and result in further impairment of cardiac function.

@article{Lohse1996b, abstract = {beta-Adrenergic receptors are often studied as prototypes of the large family of G-protein-coupled receptors, which includes many other well-known members such as the muscarinic acetylcholine receptors, but also the receptors for light, taste and olfaction. These receptors are regulated by multiple mechanisms which can affect either their function or their expression to a rapidly changing environment. The most obvious changes are effected by receptor agonists, and this process is called receptor desensitization. On the functional level, the most intriguing and important mechanism of desensitization involves the phosphorylation of beta-adrenergic and homologous receptors by specific receptor kinases, termed the G-protein-coupled receptor kinases (GRKs). This phosphorylation is followed by binding of arrestins to the receptors, which causes uncoupling of receptors and G-proteins and thus results in a loss of receptor function. On the expression level, there appear to be two major pathways leading to a reduction of the receptor number: degradation of the receptors themselves, or reduced receptor synthesis brought about by reduced receptor mRNA levels. Heart failure is accompanied by a markedly reduced responsiveness of the beta-adrenergic receptor system, which in many ways resembles the phenomena seen in agonist-induced receptor desensitization. The levels of beta 1-adrenergic receptors are reduced, and this reduction is paralleled by similar decreases in the levels of the corresponding mRNA. At the same time, the activity and the mRNA levels of one of the GRK-isoforms, GRK2 (which is identical to the beta-adrenergic receptor kinase 1) are increased. These alterations may contribute to the loss of beta-adrenergic receptor responsiveness in heart failure and result in further impairment of cardiac function.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Lohse, M. J. and Engelhardt, S. and Danner, S. and Bohm, M.}, biburl = {https://www.bibsonomy.org/bibtex/27f33e2ff34055601c70b1524feb18046/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {ee3631376ead661c6bd096d433f87512}, intrahash = {7f33e2ff34055601c70b1524feb18046}, issn = {0300-8428 (Print) 0300-8428 (Linking)}, journal = {Basic Res Cardiol}, keywords = {Animals Arrestins/metabolism Biology Failure/*metabolism GTP-Binding Heart Humans Messenger/*metabolism Molecular Phosphorylation Phosphotransferases/metabolism Proteins/metabolism RNA, Signal Transduction/*physiology beta/genetics/*metabolism Receptor Adrenergic}, note = {Lohse, M J Engelhardt, S Danner, S Bohm, M Research Support, Non-U.S. Gov't Review Germany Basic research in cardiology Basic Res Cardiol. 1996;91 Suppl 2:29-34.}, pages = {29-34}, shorttitle = {Mechanisms of beta-adrenergic receptor desensitization: from molecular biology to heart failure}, timestamp = {2010-12-14T18:22:41.000+0100}, title = {Mechanisms of beta-adrenergic receptor desensitization: from molecular biology to heart failure}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8957541}, volume = {91 Suppl 2}, year = 1996 }