%0 Journal Article %1 Liliom2001 %A Liliom, K. %A Sun, G. %A Bunemann, M. %A Virag, T. %A Nusser, N. %A Baker, D. L. %A Wang, D. A. %A Fabian, M. J. %A Brandts, B. %A Bender, K. %A Eickel, A. %A Malik, K. U. %A Miller, D. D. %A Desiderio, D. M. %A Tigyi, G. %A Pott, L. %D 2001 %J Biochem J %K & Animals Atria/metabolism Blotting, Carrier Chain Desorption-Ionization Heart Heart/*physiology Laser Mass, Matrix-Assisted Phosphorylcholine/*analogs Polymerase Precipitin Proteins/metabolism/*physiology Rabbits Rats Reaction Reverse Spectrometry, Sphingolipids/*metabolism Sphingosine/*analogs Tests Transcriptase Western derivatives/*blood %N Pt 1 %P 189-97 %T Sphingosylphosphocholine is a naturally occurring lipid mediator in blood plasma: a possible role in regulating cardiac function via sphingolipid receptors %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11256963 %V 355 %X Blood plasma and serum contain factors that activate inwardly rectifying GIRK1/GIRK4 K+ channels in atrial myocytes via one or more non-atropine-sensitive receptors coupled to pertussis-toxin-sensitive G-proteins. This channel is also the target of muscarinic M(2) receptors activated by the physiological release of acetylcholine from parasympathetic nerve endings. By using a combination of HPLC and TLC techniques with matrix-assisted laser desorption ionization-time-of-flight MS, we purified and identified sphingosine 1-phosphate (SPP) and sphingosylphosphocholine (SPC) as the plasma and serum factors responsible for activating the inwardly rectifying K+ channel (I(K)). With the use of MS the concentration of SPC was estimated at 50 nM in plasma and 130 nM in serum; those concentrations exceeded the 1.5 nM EC(50) measured in guinea-pig atrial myocytes. With the use of reverse-transcriptase-mediated PCR and/or Western blot analysis, we detected Edg1, Edg3, Edg5 and Edg8 as well as OGR1 sphingolipid receptor transcripts and/or proteins. In perfused guinea-pig hearts, SPC exerted a negative chronotropic effect with a threshold concentration of 1 microM. SPC was completely removed after perfusion through the coronary circulation at a concentration of 10 microM. On the basis of their constitutive presence in plasma, the expression of specific receptors, and a mechanism of ligand inactivation, we propose that SPP and SPC might have a physiologically relevant role in the regulation of the heart.

@article{Liliom2001, abstract = {Blood plasma and serum contain factors that activate inwardly rectifying GIRK1/GIRK4 K+ channels in atrial myocytes via one or more non-atropine-sensitive receptors coupled to pertussis-toxin-sensitive G-proteins. This channel is also the target of muscarinic M(2) receptors activated by the physiological release of acetylcholine from parasympathetic nerve endings. By using a combination of HPLC and TLC techniques with matrix-assisted laser desorption ionization-time-of-flight MS, we purified and identified sphingosine 1-phosphate (SPP) and sphingosylphosphocholine (SPC) as the plasma and serum factors responsible for activating the inwardly rectifying K+ channel (I(K)). With the use of MS the concentration of SPC was estimated at 50 nM in plasma and 130 nM in serum; those concentrations exceeded the 1.5 nM EC(50) measured in guinea-pig atrial myocytes. With the use of reverse-transcriptase-mediated PCR and/or Western blot analysis, we detected Edg1, Edg3, Edg5 and Edg8 as well as OGR1 sphingolipid receptor transcripts and/or proteins. In perfused guinea-pig hearts, SPC exerted a negative chronotropic effect with a threshold concentration of 1 microM. SPC was completely removed after perfusion through the coronary circulation at a concentration of 10 microM. On the basis of their constitutive presence in plasma, the expression of specific receptors, and a mechanism of ligand inactivation, we propose that SPP and SPC might have a physiologically relevant role in the regulation of the heart.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Liliom, K. and Sun, G. and Bunemann, M. and Virag, T. and Nusser, N. and Baker, D. L. and Wang, D. A. and Fabian, M. J. and Brandts, B. and Bender, K. and Eickel, A. and Malik, K. U. and Miller, D. D. and Desiderio, D. M. and Tigyi, G. and Pott, L.}, biburl = {https://www.bibsonomy.org/bibtex/285cf0ca5ab60d7f5e25b9a2a7874ad96/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {1782645a669d8b4d29709620f629a99a}, intrahash = {85cf0ca5ab60d7f5e25b9a2a7874ad96}, issn = {0264-6021 (Print) 0264-6021 (Linking)}, journal = {Biochem J}, keywords = {& Animals Atria/metabolism Blotting, Carrier Chain Desorption-Ionization Heart Heart/*physiology Laser Mass, Matrix-Assisted Phosphorylcholine/*analogs Polymerase Precipitin Proteins/metabolism/*physiology Rabbits Rats Reaction Reverse Spectrometry, Sphingolipids/*metabolism Sphingosine/*analogs Tests Transcriptase Western derivatives/*blood}, month = {Apr 1}, note = {Liliom, K Sun, G Bunemann, M Virag, T Nusser, N Baker, D L Wang, D A Fabian, M J Brandts, B Bender, K Eickel, A Malik, K U Miller, D D Desiderio, D M Tigyi, G Pott, L D RR 10522/RR/NCRR NIH HHS/United States HL61649/HL/NHLBI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. England The Biochemical journal Biochem J. 2001 Apr 1;355(Pt 1):189-97.}, number = {Pt 1}, pages = {189-97}, shorttitle = {Sphingosylphosphocholine is a naturally occurring lipid mediator in blood plasma: a possible role in regulating cardiac function via sphingolipid receptors}, timestamp = {2010-12-14T18:12:20.000+0100}, title = {Sphingosylphosphocholine is a naturally occurring lipid mediator in blood plasma: a possible role in regulating cardiac function via sphingolipid receptors}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11256963}, volume = 355, year = 2001 }