Sphingosylphosphocholine is a naturally occurring lipid mediator in blood plasma

A possible role in regulating cardiac function via sphingolipid receptors

K. Liliom, G. Sun, M. Bünemann, T. Virág, N. Nusser, D. L. Baker, D. A. Wang, M. J. Fabian, B. Brandts, K. Bender, A. Eickel, K. U. Malik, D. D. Miller, D. M. Desiderio, G. Tigyi, L. Pott

Research output: Contribution to journalArticle

134 Citations (Scopus)

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 M2 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 (IK). 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 EC50 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 μM. SPC was completely removed after perfusion through the coronary circulation at a concentration of 10 μM. 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.

Original languageEnglish
Pages (from-to)189-197
Number of pages9
JournalBiochemical Journal
Volume355
Issue number1
DOIs
Publication statusPublished - Apr 1 2001

Fingerprint

Sphingolipids
Blood
Lipids
Plasmas
Muscle Cells
Guinea Pigs
Serum
Muscarinic M2 Receptors
Inwardly Rectifying Potassium Channel
Coronary Circulation
Nerve Endings
RNA-Directed DNA Polymerase
Pertussis Toxin
Reverse Transcriptase Polymerase Chain Reaction
GTP-Binding Proteins
Acetylcholine
Ionization
Desorption
Lasers
Perfusion

Keywords

  • Edg receptor
  • GIRK
  • Lysosphingomyelin
  • OGR-1

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sphingosylphosphocholine is a naturally occurring lipid mediator in blood plasma : A possible role in regulating cardiac function via sphingolipid receptors. / Liliom, K.; Sun, G.; Bünemann, M.; Virág, 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.

In: Biochemical Journal, Vol. 355, No. 1, 01.04.2001, p. 189-197.

Research output: Contribution to journalArticle

Liliom, K, Sun, G, Bünemann, M, Virág, T, Nusser, N, Baker, DL, Wang, DA, Fabian, MJ, Brandts, B, Bender, K, Eickel, A, Malik, KU, Miller, DD, Desiderio, DM, Tigyi, G & Pott, L 2001, 'Sphingosylphosphocholine is a naturally occurring lipid mediator in blood plasma: A possible role in regulating cardiac function via sphingolipid receptors', Biochemical Journal, vol. 355, no. 1, pp. 189-197. https://doi.org/10.1042/0264-6021:3550189
Liliom, K. ; Sun, G. ; Bünemann, M. ; Virág, 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. / Sphingosylphosphocholine is a naturally occurring lipid mediator in blood plasma : A possible role in regulating cardiac function via sphingolipid receptors. In: Biochemical Journal. 2001 ; Vol. 355, No. 1. pp. 189-197.
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