%0 Journal Article %1 Bunemann2001 %A Bunemann, M. %A Bucheler, M. M. %A Philipp, M. %A Lohse, M. J. %A Hein, L. %D 2001 %J J Biol Chem %K *Potassium Action Activation Animals Assay Binding Calcium Cell Channels Channels, Channels/*chemistry/metabolism Channels/metabolism Dose-Response Drug Electrophysiology Enzyme Factors Fluorescence G GTP-Binding Humans Inwardly Inwardly-Rectifying Kinetics Knockout Line Mice Microscopy, Norepinephrine/metabolism/pharmacology Potassium Potentials Protein Protein-Coupled Proteins/metabolism Radioligand Rectifying Relationship, Signal Time Transduction Transfection alpha-2/*chemistry/*metabolism alpha/metabolism Receptor Adrenergic %N 50 %P 47512-7 %T Activation and deactivation kinetics of alpha 2A- and alpha 2C-adrenergic receptor-activated G protein-activated inwardly rectifying K+ channel currents %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11591725 %V 276 %X Although G protein-coupled receptor-mediated signaling is one of the best studied biological events, little is known about the kinetics of these processes in intact cells. Experiments with neurons from alpha(2A)-adrenergic receptor knockout mice suggested that the alpha(2A)-receptor subtype inhibits neurotransmitter release with higher speed and at higher action potential frequencies than the alpha(2C)-adrenergic receptor. Here we investigated whether these functional differences between presynaptic alpha(2)-adrenergic receptor subtypes are the result of distinct signal transduction kinetics of these two receptors and their coupling to G proteins. alpha(2A)- and alpha(2C)-receptors were stably expressed in HEK293 cells at moderate ( approximately 2 pmol/mg) or high (17-24 pmol/mg) levels. Activation of G protein-activated inwardly rectifying K(+) (GIRK) channels was similar in extent and kinetics for alpha(2A)- and alpha(2C)-receptors at both expression levels. However, the two receptors differed significantly in their deactivation kinetics after removal of the agonist norepinephrine. alpha(2C)-Receptor-activated GIRK currents returned much more slowly to base line than did alpha(2A)-stimulated currents. This observation correlated with a higher affinity of norepinephrine at the murine alpha(2C)- than at the alpha(2A)-receptor subtype and may explain why alpha(2C)-adrenergic receptors are especially suited to control sympathetic neurotransmission at low action potential frequencies in contrast to the alpha(2A)-receptor subtype.

@article{Bunemann2001, abstract = {Although G protein-coupled receptor-mediated signaling is one of the best studied biological events, little is known about the kinetics of these processes in intact cells. Experiments with neurons from alpha(2A)-adrenergic receptor knockout mice suggested that the alpha(2A)-receptor subtype inhibits neurotransmitter release with higher speed and at higher action potential frequencies than the alpha(2C)-adrenergic receptor. Here we investigated whether these functional differences between presynaptic alpha(2)-adrenergic receptor subtypes are the result of distinct signal transduction kinetics of these two receptors and their coupling to G proteins. alpha(2A)- and alpha(2C)-receptors were stably expressed in HEK293 cells at moderate ( approximately 2 pmol/mg) or high (17-24 pmol/mg) levels. Activation of G protein-activated inwardly rectifying K(+) (GIRK) channels was similar in extent and kinetics for alpha(2A)- and alpha(2C)-receptors at both expression levels. However, the two receptors differed significantly in their deactivation kinetics after removal of the agonist norepinephrine. alpha(2C)-Receptor-activated GIRK currents returned much more slowly to base line than did alpha(2A)-stimulated currents. This observation correlated with a higher affinity of norepinephrine at the murine alpha(2C)- than at the alpha(2A)-receptor subtype and may explain why alpha(2C)-adrenergic receptors are especially suited to control sympathetic neurotransmission at low action potential frequencies in contrast to the alpha(2A)-receptor subtype.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Bunemann, M. and Bucheler, M. M. and Philipp, M. and Lohse, M. J. and Hein, L.}, biburl = {https://www.bibsonomy.org/bibtex/2c0062dd6eec6dd04dee7234057a5aa5c/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {c50b8ff3e51d0fb2d4d2a5025dc81b5d}, intrahash = {c0062dd6eec6dd04dee7234057a5aa5c}, issn = {0021-9258 (Print) 0021-9258 (Linking)}, journal = {J Biol Chem}, keywords = {*Potassium Action Activation Animals Assay Binding Calcium Cell Channels Channels, Channels/*chemistry/metabolism Channels/metabolism Dose-Response Drug Electrophysiology Enzyme Factors Fluorescence G GTP-Binding Humans Inwardly Inwardly-Rectifying Kinetics Knockout Line Mice Microscopy, Norepinephrine/metabolism/pharmacology Potassium Potentials Protein Protein-Coupled Proteins/metabolism Radioligand Rectifying Relationship, Signal Time Transduction Transfection alpha-2/*chemistry/*metabolism alpha/metabolism Receptor Adrenergic}, month = {Dec 14}, note = {Bunemann, M Bucheler, M M Philipp, M Lohse, M J Hein, L Research Support, Non-U.S. Gov't United States The Journal of biological chemistry J Biol Chem. 2001 Dec 14;276(50):47512-7. Epub 2001 Oct 8.}, number = 50, pages = {47512-7}, shorttitle = {Activation and deactivation kinetics of alpha 2A- and alpha 2C-adrenergic receptor-activated G protein-activated inwardly rectifying K+ channel currents}, timestamp = {2010-12-14T18:22:38.000+0100}, title = {Activation and deactivation kinetics of alpha 2A- and alpha 2C-adrenergic receptor-activated G protein-activated inwardly rectifying K+ channel currents}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11591725}, volume = 276, year = 2001 }