Detection of the full-length transcript variant for neurokinin-1 receptor in human whole blood associated with enhanced reinforcement of clot by substance-P.

Toshiharu Azma, Yuki Sugimoto, Hiroyuki Kinoshita, Taishin Ito, Masanori Tsukamoto, Hiroshi Hoshijima, Masakazu Nakao, Hirosato Kikuchi

Department of Anesthesiology, Faculty of Medicine, Saitama Medical University, Iruma-gun, Saitama, Japan. azmacci@nifty.com

Journal of thrombosis and thrombolysis 2012 May

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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.

Citation

Toshiharu Azma, Yuki Sugimoto, Hiroyuki Kinoshita, Taishin Ito, Masanori Tsukamoto, Hiroshi Hoshijima, Masakazu Nakao, Hirosato Kikuchi. Detection of the full-length transcript variant for neurokinin-1 receptor in human whole blood associated with enhanced reinforcement of clot by substance-P. Journal of thrombosis and thrombolysis. 2012 May;33(4):329-37