Sphingosylphosphocholine is a naturally occurring lipid mediator in blood plasma: a possible role in regulating cardiac function via sphingolipid receptors.
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.
Liliom
K
K
Department of Physiology, The University of Tennessee Health Sciences Center, Memphis, TN 38163, U.S.A.
Sun
G
G
Bünemann
M
M
Virág
T
T
Nusser
N
N
Baker
D L
DL
Wang
D A
DA
Fabian
M J
MJ
Brandts
B
B
Bender
K
K
Eickel
A
A
Malik
K U
KU
Miller
D D
DD
Desiderio
D M
DM
Tigyi
G
G
Pott
L
L
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006325:Heart Atria / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000097:blood*; D011233:Precipitin Tests; D011817:Rabbits; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013107:Sphingolipids / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood*
D002352:Carrier Proteins; D013107:Sphingolipids; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D013110:Sphingosine