%0 Journal Article %1 Warrier2007 %A Warrier, S. %A Ramamurthy, G. %A Eckert, R. L. %A Nikolaev, V. O. %A Lohse, M. J. %A Harvey, R. D. %D 2007 %J J Physiol %K AMP/*physiology Adrenergic Alprostadil/pharmacology Animals Calcium Cardiac/*metabolism Caveolae/metabolism Channels, Cultured Cyclic Cytosol/metabolism Diester Distribution/drug GTP-Binding Gi-Go/physiology Guinea Heart Hydrolases/metabolism Isoproterenol/pharmacology L-Type/drug Myocytes, Phosphoric Pigs Prostaglandin/metabolism Protein Structure, Subunits, Tertiary Tissue Ventricles alpha beta-Agonists/pharmacology effects effects/*metabolism Receptor Cell %N Pt.3 %P 765-76 %T cAMP microdomains and L-type Ca2+ channel regulation in guinea-pig ventricular myocytes %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17289786 %V 580 %X Many different receptors can stimulate cAMP synthesis in the heart, but not all elicit the same functional responses. For example, it has been recognized for some time that prostaglandins such as PGE1 increase cAMP production and activate PKA, but they do not elicit responses like those produced by beta-adrenergic receptor (betaAR) agonists such as isoproterenol (isoprenaline), even though both stimulate the same signalling pathway. In the present study, we confirm that isoproterenol, but not PGE1, is able to produce cAMP-dependent stimulation of the L-type Ca(2+) current in guinea pig ventricular myocytes. This is despite finding evidence that these cells express EP(4) prostaglandin receptors, which are known to activate G(s)-dependent signalling pathways. Using fluorescence resonance energy transfer-based biosensors that are either freely diffusible or bound to A kinase anchoring proteins, we demonstrate that the difference is due to the ability of isoproterenol to stimulate cAMP production in cytosolic and caveolar compartments of intact cardiac myocytes, while PGE1 only stimulates cAMP production in the cytosolic compartment. Unlike other receptor-mediated responses, compartmentation of PGE1 responses was not due to concurrent activation of a G(i)-dependent signalling pathway or phosphodiesterase activity. Instead, compartmentation of the PGE1 response in cardiac myocytes appears to be due to transient stimulation of cAMP in a microdomain that can communicate directly with the bulk cytosolic compartment but not the caveolar compartment associated with betaAR regulation of L-type Ca(2+) channel function.

@article{Warrier2007, abstract = {Many different receptors can stimulate cAMP synthesis in the heart, but not all elicit the same functional responses. For example, it has been recognized for some time that prostaglandins such as PGE1 increase cAMP production and activate PKA, but they do not elicit responses like those produced by beta-adrenergic receptor (betaAR) agonists such as isoproterenol (isoprenaline), even though both stimulate the same signalling pathway. In the present study, we confirm that isoproterenol, but not PGE1, is able to produce cAMP-dependent stimulation of the L-type Ca(2+) current in guinea pig ventricular myocytes. This is despite finding evidence that these cells express EP(4) prostaglandin receptors, which are known to activate G(s)-dependent signalling pathways. Using fluorescence resonance energy transfer-based biosensors that are either freely diffusible or bound to A kinase anchoring proteins, we demonstrate that the difference is due to the ability of isoproterenol to stimulate cAMP production in cytosolic and caveolar compartments of intact cardiac myocytes, while PGE1 only stimulates cAMP production in the cytosolic compartment. Unlike other receptor-mediated responses, compartmentation of PGE1 responses was not due to concurrent activation of a G(i)-dependent signalling pathway or phosphodiesterase activity. Instead, compartmentation of the PGE1 response in cardiac myocytes appears to be due to transient stimulation of cAMP in a microdomain that can communicate directly with the bulk cytosolic compartment but not the caveolar compartment associated with betaAR regulation of L-type Ca(2+) channel function.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Warrier, S. and Ramamurthy, G. and Eckert, R. L. and Nikolaev, V. O. and Lohse, M. J. and Harvey, R. D.}, biburl = {https://www.bibsonomy.org/bibtex/24e1140c92164cf73c4751a811938f723/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {e7057f4c9ce12451b64f7c65a6a443cc}, intrahash = {4e1140c92164cf73c4751a811938f723}, issn = {0022-3751 (Print) 0022-3751 (Linking)}, journal = {J Physiol}, keywords = {AMP/*physiology Adrenergic Alprostadil/pharmacology Animals Calcium Cardiac/*metabolism Caveolae/metabolism Channels, Cultured Cyclic Cytosol/metabolism Diester Distribution/drug GTP-Binding Gi-Go/physiology Guinea Heart Hydrolases/metabolism Isoproterenol/pharmacology L-Type/drug Myocytes, Phosphoric Pigs Prostaglandin/metabolism Protein Structure, Subunits, Tertiary Tissue Ventricles alpha beta-Agonists/pharmacology effects effects/*metabolism Receptor Cell}, month = {May 1}, note = {Warrier, Sunita Ramamurthy, Gopalakrishnan Eckert, Richard L Nikolaev, Viacheslav O Lohse, Martin J Harvey, Robert D Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England The Journal of physiology J Physiol. 2007 May 1;580(Pt.3):765-76. Epub 2007 Feb 8.}, number = {Pt.3}, pages = {765-76}, shorttitle = {cAMP microdomains and L-type Ca2+ channel regulation in guinea-pig ventricular myocytes}, timestamp = {2010-12-14T18:20:51.000+0100}, title = {cAMP microdomains and L-type Ca2+ channel regulation in guinea-pig ventricular myocytes}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17289786}, volume = 580, year = 2007 }