A novel membrane receptor with high affinity for lysosphingomyelin
and sphingosine 1-phosphate in atrial myocytes
M. Bunemann, K. Liliom, B. Brandts, L. Pott, J. Tseng, D. Desiderio, G. Sun, D. Miller, und G. Tigyi. EMBO J, 15 (20):
5527-34(Oktober 1996)Bunemann, M Liliom, K Brandts, B K Pott, L Tseng, J L Desiderio,
D M Sun, G Miller, D Tigyi, G Research Support, Non-U.S. Gov't Research
Support, U.S. Gov't, Non-P.H.S. England The EMBO journal EMBO J.
1996 Oct 15;15(20):5527-34..
Zusammenfassung
Activation of IK(ACh) is the major effect of the vagal neutrotransmitter
acetylcholine in the heart. We report that both lysosphingomyelin
(D-erythro-sphingosyl-phosphorylcholine; SPC) and sphingosine 1-phosphate
(SPP) activate IK(ACh) in guinea pig atrial myocytes through the
same receptor with an EC50 of 1.5 and 1.2 nM, respectively. Pertussis
toxin abolished the activation of IK(ACh) by either lipid. The putative
receptor showed an exquisite stereoselectivity for the naturally
occurring D-erythro-(2S,3R)-SPC stereoisomer, the structure of which
was confirmed by mass spectroscopy and NMR. These lipids caused complete
homologous and heterologous desensitization with each other but not
with ACh, indicating that both act on the same receptor. This receptor
displays a distinct structure-activity relationship: it requires
an unsubstituted amino group because N-acetyl-SPC, lysophosphatidic
acid and lysophosphatidylcholine were inactive. Because SPP and SPC
are naturally occurring products of membrane lipid metabolism, it
appears that these compounds might be important extracellular mediators
acting on a family of bona fide G protein-coupled receptors. Expression
of these receptors in the heart raises the possibility that sphingolipids
may be a part of the physiological and/or pathophysiological regulation
of the heart. Based on their ligand selectivity we propose a classification
of the sphingolipid receptors.
Bunemann, M Liliom, K Brandts, B K Pott, L Tseng, J L Desiderio,
D M Sun, G Miller, D Tigyi, G Research Support, Non-U.S. Gov't Research
Support, U.S. Gov't, Non-P.H.S. England The EMBO journal EMBO J.
1996 Oct 15;15(20):5527-34.
%0 Journal Article
%1 Bunemann1996a
%A Bunemann, M.
%A Liliom, K.
%A Brandts, B. K.
%A Pott, L.
%A Tseng, J. L.
%A Desiderio, D. M.
%A Sun, G.
%A Miller, D.
%A Tigyi, G.
%D 1996
%J EMBO J
%K & *Lysophospholipids *Potassium Animals Atom Atria/cytology/*metabolism Bombardment Bordetella/pharmacology Channels Channels, Channels/*metabolism Electrophysiology Factors, Fast G Guinea Heart Inwardly Inwardly-Rectifying Magnetic Mass, Models, Molecular Muscarinic/*metabolism Pertussis Phosphorylcholine/*analogs Pigs Potassium Protein-Coupled Rectifying Relationship Resonance Spectrometry, Spectroscopy Sphingosine/*analogs Stereoisomerism Structure-Activity Toxin Virulence derivatives/metabolism Receptor
%N 20
%P 5527-34
%T A novel membrane receptor with high affinity for lysosphingomyelin
and sphingosine 1-phosphate in atrial myocytes
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8896446
%V 15
%X Activation of IK(ACh) is the major effect of the vagal neutrotransmitter
acetylcholine in the heart. We report that both lysosphingomyelin
(D-erythro-sphingosyl-phosphorylcholine; SPC) and sphingosine 1-phosphate
(SPP) activate IK(ACh) in guinea pig atrial myocytes through the
same receptor with an EC50 of 1.5 and 1.2 nM, respectively. Pertussis
toxin abolished the activation of IK(ACh) by either lipid. The putative
receptor showed an exquisite stereoselectivity for the naturally
occurring D-erythro-(2S,3R)-SPC stereoisomer, the structure of which
was confirmed by mass spectroscopy and NMR. These lipids caused complete
homologous and heterologous desensitization with each other but not
with ACh, indicating that both act on the same receptor. This receptor
displays a distinct structure-activity relationship: it requires
an unsubstituted amino group because N-acetyl-SPC, lysophosphatidic
acid and lysophosphatidylcholine were inactive. Because SPP and SPC
are naturally occurring products of membrane lipid metabolism, it
appears that these compounds might be important extracellular mediators
acting on a family of bona fide G protein-coupled receptors. Expression
of these receptors in the heart raises the possibility that sphingolipids
may be a part of the physiological and/or pathophysiological regulation
of the heart. Based on their ligand selectivity we propose a classification
of the sphingolipid receptors.
@article{Bunemann1996a,
abstract = {Activation of IK(ACh) is the major effect of the vagal neutrotransmitter
acetylcholine in the heart. We report that both lysosphingomyelin
(D-erythro-sphingosyl-phosphorylcholine; SPC) and sphingosine 1-phosphate
(SPP) activate IK(ACh) in guinea pig atrial myocytes through the
same receptor with an EC50 of 1.5 and 1.2 nM, respectively. Pertussis
toxin abolished the activation of IK(ACh) by either lipid. The putative
receptor showed an exquisite stereoselectivity for the naturally
occurring D-erythro-(2S,3R)-SPC stereoisomer, the structure of which
was confirmed by mass spectroscopy and NMR. These lipids caused complete
homologous and heterologous desensitization with each other but not
with ACh, indicating that both act on the same receptor. This receptor
displays a distinct structure-activity relationship: it requires
an unsubstituted amino group because N-acetyl-SPC, lysophosphatidic
acid and lysophosphatidylcholine were inactive. Because SPP and SPC
are naturally occurring products of membrane lipid metabolism, it
appears that these compounds might be important extracellular mediators
acting on a family of bona fide G protein-coupled receptors. Expression
of these receptors in the heart raises the possibility that sphingolipids
may be a part of the physiological and/or pathophysiological regulation
of the heart. Based on their ligand selectivity we propose a classification
of the sphingolipid receptors.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Bunemann, M. and Liliom, K. and Brandts, B. K. and Pott, L. and Tseng, J. L. and Desiderio, D. M. and Sun, G. and Miller, D. and Tigyi, G.},
biburl = {https://www.bibsonomy.org/bibtex/22ff9d29b0b57f92af328daef43d21637/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {529bd39c2b085151b5060d81feaa8993},
intrahash = {2ff9d29b0b57f92af328daef43d21637},
issn = {0261-4189 (Print) 0261-4189 (Linking)},
journal = {EMBO J},
keywords = {& *Lysophospholipids *Potassium Animals Atom Atria/cytology/*metabolism Bombardment Bordetella/pharmacology Channels Channels, Channels/*metabolism Electrophysiology Factors, Fast G Guinea Heart Inwardly Inwardly-Rectifying Magnetic Mass, Models, Molecular Muscarinic/*metabolism Pertussis Phosphorylcholine/*analogs Pigs Potassium Protein-Coupled Rectifying Relationship Resonance Spectrometry, Spectroscopy Sphingosine/*analogs Stereoisomerism Structure-Activity Toxin Virulence derivatives/metabolism Receptor},
month = {Oct 15},
note = {Bunemann, M Liliom, K Brandts, B K Pott, L Tseng, J L Desiderio,
D M Sun, G Miller, D Tigyi, G Research Support, Non-U.S. Gov't Research
Support, U.S. Gov't, Non-P.H.S. England The EMBO journal EMBO J.
1996 Oct 15;15(20):5527-34.},
number = 20,
pages = {5527-34},
shorttitle = {A novel membrane receptor with high affinity for lysosphingomyelin
and sphingosine 1-phosphate in atrial myocytes},
timestamp = {2010-12-14T18:20:01.000+0100},
title = {A novel membrane receptor with high affinity for lysosphingomyelin
and sphingosine 1-phosphate in atrial myocytes},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8896446},
volume = 15,
year = 1996
}