A novel membrane receptor with high affinity for lysosphingomyelin and sphingosine 1-phosphate in atrial myocytes

Moritz Bünemann, Károly Liliom, Bodo K. Brandts, Lutz Pott, Jih Lie Tseng, Dominic M. Desiderio, Guoping Sun, Duane Miller, Gabor Tigyi

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Activation of I(K(ACh)) is the major effect of the vagal neurotransmitter acetylcholine in the heart. We report that both lysosphingomyelin (D-erythro-sphingosylphosphorylcholine; SPC) and sphingosine 1-phosphate (SPP) activate I(K(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 I(K(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.

Original languageEnglish (US)
Pages (from-to)5527-5534
Number of pages8
JournalEMBO Journal
Volume15
Issue number20
StatePublished - Oct 15 1996

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Muscle Cells
Sphingolipids
Membranes
Chemical activation
Lipids
Stereoselectivity
Lysophosphatidylcholines
Stereoisomerism
Pertussis Toxin
Structure-Activity Relationship
Membrane Lipids
G-Protein-Coupled Receptors
Lipid Metabolism
Acetylcholine
Neurotransmitter Agents
Mass Spectrometry
Guinea Pigs
Nuclear magnetic resonance
Spectroscopy
Ligands

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

Cite this

Bünemann, M., Liliom, K., Brandts, B. K., Pott, L., Tseng, J. L., Desiderio, D. M., ... Tigyi, G. (1996). A novel membrane receptor with high affinity for lysosphingomyelin and sphingosine 1-phosphate in atrial myocytes. EMBO Journal, 15(20), 5527-5534.

A novel membrane receptor with high affinity for lysosphingomyelin and sphingosine 1-phosphate in atrial myocytes. / Bünemann, Moritz; Liliom, Károly; Brandts, Bodo K.; Pott, Lutz; Tseng, Jih Lie; Desiderio, Dominic M.; Sun, Guoping; Miller, Duane; Tigyi, Gabor.

In: EMBO Journal, Vol. 15, No. 20, 15.10.1996, p. 5527-5534.

Research output: Contribution to journalArticle

Bünemann, M, Liliom, K, Brandts, BK, Pott, L, Tseng, JL, Desiderio, DM, Sun, G, Miller, D & Tigyi, G 1996, 'A novel membrane receptor with high affinity for lysosphingomyelin and sphingosine 1-phosphate in atrial myocytes', EMBO Journal, vol. 15, no. 20, pp. 5527-5534.
Bünemann M, Liliom K, Brandts BK, Pott L, Tseng JL, Desiderio DM et al. A novel membrane receptor with high affinity for lysosphingomyelin and sphingosine 1-phosphate in atrial myocytes. EMBO Journal. 1996 Oct 15;15(20):5527-5534.
Bünemann, Moritz ; Liliom, Károly ; Brandts, Bodo K. ; Pott, Lutz ; Tseng, Jih Lie ; Desiderio, Dominic M. ; Sun, Guoping ; Miller, Duane ; Tigyi, Gabor. / A novel membrane receptor with high affinity for lysosphingomyelin and sphingosine 1-phosphate in atrial myocytes. In: EMBO Journal. 1996 ; Vol. 15, No. 20. pp. 5527-5534.
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