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 GI RK1/GIRK4 K+ channels in atrial myocytes via one or more non-atropine-sensi tive receptors coupled to pertussis-toxin-sensitive G-proteins, This channe l is also the target of muscarinic M-2 receptors activated by the physiolog ical release of acetylcholine from parasympathetic nerve endings. By using a combination of HPLC and TLC techniques with matrix-assisted laser desorpt ion 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 pla sma and 130 nM in serum: those concentrations exceeded the 1.5 nM EC50 meas ured in guinea-pig atrial myocytes, With the use of reverse-transcriptase-m ediated 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 muM. SPC was completely removed after perfu sion through the coronary circulation at a concentration of 10 muM. 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 hea rt.