Detection of the full-length transcript variant for neurokinin-1 receptor in human whole blood associated with enhanced reinforcement of clot by substance-P
Detection of the full-length transcript variant for neurokinin-1 receptor in human whole blood associated with enhanced reinforcement of clot by substance-P
复制标题
检测人全血中神经激肽 1 受体的全长转录变体，与 P 物质增强凝块强化相关
DOI：
10.1007/s11239-011-0650-1
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Kikuchi H
中科院分区：
文献类型：
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作者：
Azma T;Sugimoto Y;Kinoshita H;Ito T;Tsukamoto M;Hoshijima H;Nakao M;Kikuchi H
我们最近报道了用于疼痛的神经递质P物质（SP）通过神经激肽-1受体（NK 1 R）促进血小板依赖性凝块形成，其中白细胞似乎参与其中（J Thromb Thrombolysis 2009;27：280-6）。鉴定了具有不同信号转导效力的两种天然存在的NK 1 R剪接异构体，即全长和截短的NK 1 R。已知人白细胞表达截短的NK 1 R，而全长NK 1 R的体内表达尚未完全阐明。NK 1 R的选择性剪接对凝块形成的调节作用也有待评估。通过实时逆转录聚合酶链反应（RT-PCR）评价人全血（n= 20）中NK 1 R转录变体mRNA的表达。通过使用双探针粘弹性测定法，测量在含或不含SP（10 nM）和NK 1 R拮抗剂Spantide（1 μM）的柠檬酸盐全血中重新加载钙后形成的凝块强度的15 min时间序列。在20份样本中，5份样本检测到全长转录变异。SP显著增加了血凝块强度，而Spantide抑制了SP引起的变化。SP/NK 1 R途径在表达全长转录变体的亚组中的调节程度是另一个没有表达的亚组中的调节程度的三倍。我们的结论是，NK 1 R的全长转录变体的表达可以在人全血中检测到，这种表达与增强增强凝块由SP。需要进一步的研究提名这种mRNA作为生物标志物的血栓前风险在痛苦的条件下，如围手术期。
We have recently reported that a neurotransmitter for pain, substance-P (SP), promotes platelet-dependent clot formation through neurokinin-1 receptors (NK1Rs), in which leukocytes appear to be involved (J Thromb Thrombolysis 2009;27:280–6). Two naturally occurring splice isoforms of NK1R with different signal transduction potency, namely the full-length and the truncated NK1Rs are identified. It is known that human leukocytes express truncated NK1Rs, while in vivo expression of the full-length NK1R has not yet been fully clarified. Modulatory effects of alternative splicing for NK1Rs on clot formation also remain to be evaluated. Expression of the transcript variant mRNA for NK1Rs in human whole blood (n= 20) was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR). A 15 min time series of the strength of clot, formed after reloading of calcium in citrated whole blood with or without SP (10 nM) and a NK1R antagonist Spantide (1 μM), was measured by using oscillating-probe viscoelastometry. The full-length transcript variant was detected in 5 samples among 20. SP significantly increased the clot strength while Spantide suppressed the SP-derived change. The extent of modulation by SP/NK1R pathway in a subgroup with expression of the full-length transcript variant was three times as potent as those in another subgroup without expression. We conclude that expression of the full-length transcript variant for NK1R can be detected in human whole blood and that such expression is associated with the enhanced reinforcement of clot by SP. Further study is required to nominate this mRNA as a biomarker for prothrombotic risks in painful conditions such as perioperative period.