%0 Journal Article %1 Bunemann2001a %A Bunemann, M. %A Hosey, M. M. %D 2001 %J Life Sci %K *Potassium 5'-O-(3-Thiotriphosphate)/pharmacology Acetylcholine/pharmacology Animals CHO Calcium Channels Channels, Channels/genetics/*metabolism Cricetinae Cultured G GTP-Binding Guanosine Heterotrimeric Humans Inwardly Inwardly-Rectifying M2 M3 M4 Muscarinic Muscarinic/genetics/*metabolism N-Type/metabolism P1/metabolism Patch-Clamp Potassium Protein-Coupled Purinergic Rectifying Signal Techniques Transduction/drug Transfection effects/*physiology Receptor Cell Proteins/metabolism %N 22-23 %P 2525-33 %T Novel signalling events mediated by muscarinic receptor subtypes %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11392622 %V 68 %X The M2 muscarinic acetylcholine receptor (mAChR) activates Gi protein coupled pathways, such as stimulation of G-protein activated inwardly rectifying K channels (GIRKs). Here we report a novel heterologous desensitization of these GIRK currents, which appeared to be specifically induced by M2/M4 mAChR stimulation, but not via adenosine (Ado) and alpha2-adrenergic receptors (AR). This heterologous desensitization reflected an inhibition of the GIRK signalling pathway downstream of G-protein activation. It was mediated in a membrane-delimited fashion via a PTX insensitive GTP dependent pathway and could be competed with exogenous Gbetagamma. The activation of M3 mAChR/Gq coupled receptors potently inhibited GIRK currents similar as M2 mAChR. By monitoring simultaneously the response of A1 adenosine receptor (AdoR) activation on N-type Ca2+ channels and GIRK channels, the stimulation of M3 mAChR was found to cause an inhibition of the Ado response in both effector systems, suggesting that the inhibition occurred at the level of the G-protein common to both effectors. These results indicated that Gq proteins inhibit pathways that are commonly regulated by Gbetagamma proteins.

@article{Bunemann2001a, abstract = {The M2 muscarinic acetylcholine receptor (mAChR) activates Gi protein coupled pathways, such as stimulation of G-protein activated inwardly rectifying K channels (GIRKs). Here we report a novel heterologous desensitization of these GIRK currents, which appeared to be specifically induced by M2/M4 mAChR stimulation, but not via adenosine (Ado) and alpha2-adrenergic receptors (AR). This heterologous desensitization reflected an inhibition of the GIRK signalling pathway downstream of G-protein activation. It was mediated in a membrane-delimited fashion via a PTX insensitive GTP dependent pathway and could be competed with exogenous Gbetagamma. The activation of M3 mAChR/Gq coupled receptors potently inhibited GIRK currents similar as M2 mAChR. By monitoring simultaneously the response of A1 adenosine receptor (AdoR) activation on N-type Ca2+ channels and GIRK channels, the stimulation of M3 mAChR was found to cause an inhibition of the Ado response in both effector systems, suggesting that the inhibition occurred at the level of the G-protein common to both effectors. These results indicated that Gq proteins inhibit pathways that are commonly regulated by Gbetagamma proteins.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Bunemann, M. and Hosey, M. M.}, biburl = {https://www.bibsonomy.org/bibtex/2a4a11152cf030d2849b2c0dccd4c92ac/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {57704192a6117cadab706b22531f1d73}, intrahash = {a4a11152cf030d2849b2c0dccd4c92ac}, issn = {0024-3205 (Print) 0024-3205 (Linking)}, journal = {Life Sci}, keywords = {*Potassium 5'-O-(3-Thiotriphosphate)/pharmacology Acetylcholine/pharmacology Animals CHO Calcium Channels Channels, Channels/genetics/*metabolism Cricetinae Cultured G GTP-Binding Guanosine Heterotrimeric Humans Inwardly Inwardly-Rectifying M2 M3 M4 Muscarinic Muscarinic/genetics/*metabolism N-Type/metabolism P1/metabolism Patch-Clamp Potassium Protein-Coupled Purinergic Rectifying Signal Techniques Transduction/drug Transfection effects/*physiology Receptor Cell Proteins/metabolism}, month = {Apr 27}, note = {Bunemann, M Hosey, M M HL50121/HL/NHLBI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England Life sciences Life Sci. 2001 Apr 27;68(22-23):2525-33.}, number = {22-23}, pages = {2525-33}, shorttitle = {Novel signalling events mediated by muscarinic receptor subtypes}, timestamp = {2010-12-14T18:21:42.000+0100}, title = {Novel signalling events mediated by muscarinic receptor subtypes}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11392622}, volume = 68, year = 2001 }