Sphingosylphosphocholine is a naturally occurring lipid mediator in blood plasma:: a possible role in regulating cardiac function via sphingolipid receptors
Sphingosylphosphocholine is a naturally occurring lipid mediator in blood plasma:: a possible role in regulating cardiac function via sphingolipid receptors
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DOI：
10.1042/0264-6021:3550189
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发表时间：
2001-04-01
影响因子：
4.1
通讯作者：
Pott, L
中科院分区：
文献类型：
--
作者：
Liliom, K;Sun, GP;Pott, L
血浆和血清含有通过一种或多种与百日咳毒素敏感性G蛋白偶联的非阿托品敏感性受体激活心房肌细胞中的内向整流GIRK 1/GIRK 4 K+通道的因子。该通道也是由副交感神经末梢生理性释放乙酰胆碱激活的毒蕈碱M-2受体的靶点。采用高效液相色谱（HPLC）和薄层色谱（TLC）结合基质辅助激光解吸电离飞行时间质谱（MS）技术，我们纯化并鉴定了1-磷酸鞘氨醇（SPP）和鞘氨酰磷酸胆碱（SPC）作为血浆和血清中激活内向整流钾通道（I-K）的因子。使用MS估计SPC的浓度在血浆中为50 nM，在血清中为130 nM：这些浓度超过了在豚鼠心房肌细胞中测量的1.5 nM EC 50。使用逆转录酶介导的PCR和/或Western印迹分析，我们检测到Edg 1，Edg 3，Edg 5和Edg 8以及OGR 1鞘脂受体转录物和/或蛋白。在灌流豚鼠心脏，SPC发挥负性变时作用的阈值浓度为1 μ M。SPC在以10 μ M的浓度通过冠状循环灌注后被完全去除。基于它们在血浆中的组成性存在，特异性受体的表达。和配体失活的机制，我们建议，SPP和SPC可能有生理相关的作用，在调节心脏。
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 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 muM. SPC was completely removed after perfusion 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 heart.