Localization of neurokinin 1 receptor (NK1R), the endogenous receptor for neuropeptide substance P (SP), has already been described for the right atrium (RA) of the heart. However, the biological role of SP/NK1R signal pathways in the RA remains unclear. Sprague-Dawley rats were randomly divided into 4 groups (n = 22 each); subjected to sham, ischemia/reperfusion-injury (I/R), I/R with 5 nmole/kg SP injection (SP + I/R), and SP + I/R with 1 mg/kg RP67580 injection (RP, a selective non-peptide tachykinin NK1R antagonist) (RP/SP + I/R). The left anterior descending coronary artery was occluded for 40 min followed by 1 day reperfusion with SP or SP + RP or without either. After 1 day, both atria and ventricles as well as the heart apexes were collected. SP promoted the expression of c-Kit, GATA4, Oct4, Nanog, and Sox2 in only the RA of the SP + I/R rats via NK1R activation. In agreement with these observations, NK1R-expressing c-Kit+ Nkx2.5+GATA4+ cardiac progenitor cells (CPCs) in the ex vivo RA explant outgrowth assay markedly migrated out from RA1 day SP + I/R approximately 2-fold increase more than RA1 day I/R. Treatment of SP promoted proliferation, migration, cardiosphere formation, and potential to differentiate into cardiomyocytes. Using RP inhibitor, NK1R antagonist not only inhibited cell proliferation and migration but also reduced the formation of cardiosphere and differentiation of c-Kit+ CPCs. SP/NK1R might play a role as a key mediator involved in the cellular response to c-Kit+ CPC expansion in RA of the heart within 24 h after I/R.

中文翻译：

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P物质增强缺血/再灌注损伤心脏右心房中表达NK1R的c-kit +心脏祖细胞的局部活化。

神经激肽1受体（NK1R）是神经肽物质P（SP）的内源性受体，已经在心脏的右心房（RA）中进行了定位。但是，尚不清楚RA​​中SP / NK1R信号通路的生物学作用。将Sprague-Dawley大鼠随机分为4组（每组22只）。接受假手术，缺血/再灌注损伤（I / R），以5 nmole / kg SP注射（SP + I / R）进行I / R和以1 mg / kg RP67580注射进行SP + I / R（RP，a选择性非肽速激肽NK1R拮抗剂（RP / SP + I / R）。闭塞左冠状动脉前降支40分钟，然后再用SP或SP + RP或不使用二者再灌注1天。1天后，收集心房和心室以及心脏顶点。SP促进了c-Kit，GATA4，Oct4，Nanog，SP + I / R大鼠的RA中只有NK1R和Sox2通过NK1R激活。与这些观察结果一致，离体RA外植体生长试验中表达NK1R的c-Kit + Nkx2.5 + GATA4 +心脏祖细胞（CPC）从RA1天SP + I / R明显移出，比RA1多2倍。第一天 SP的治疗促进了增殖，迁移，心球形成以及分化为心肌细胞的潜力。使用RP抑制剂，NK1R拮抗剂不仅抑制细胞增殖和迁移，而且减少了心球的形成和c-Kit + CPC的分化。在I / R后24小时内，SP / NK1R可能是参与细胞对心脏RA中c-Kit + CPC扩增的细胞应答的关键介体。离体RA外植体生长试验中的5 + GATA4 +心脏祖细胞（CPC）从RA1天SP + I / R显着移出，比RA1天I / R增加约2倍。SP的治疗促进了增殖，迁移，心球形成以及分化为心肌细胞的潜力。使用RP抑制剂，NK1R拮抗剂不仅抑制细胞增殖和迁移，而且减少了心球的形成和c-Kit + CPC的分化。在I / R后24小时内，SP / NK1R可能是参与细胞对心脏RA中c-Kit + CPC扩增的细胞应答的关键介体。离体RA外植体生长试验中的5 + GATA4 +心脏祖细胞（CPC）从RA1天SP + I / R显着移出，比RA1天I / R增加约2倍。SP的治疗促进了增殖，迁移，心球形成以及分化为心肌细胞的潜力。使用RP抑制剂，NK1R拮抗剂不仅抑制细胞增殖和迁移，而且减少了心球的形成和c-Kit + CPC的分化。在I / R后24小时内，SP / NK1R可能是参与细胞对心脏RA中c-Kit + CPC扩增的细胞应答的关键介体。并具有分化为心肌细胞的潜力。使用RP抑制剂，NK1R拮抗剂不仅抑制细胞增殖和迁移，而且减少了心球的形成和c-Kit + CPC的分化。在I / R后24小时内，SP / NK1R可能是参与细胞对心脏RA中c-Kit + CPC扩增的细胞应答的关键介体。并具有分化成心肌细胞的潜力。使用RP抑制剂，NK1R拮抗剂不仅抑制细胞增殖和迁移，而且减少了心球的形成和c-Kit + CPC的分化。在I / R后24小时内，SP / NK1R可能是参与细胞对心脏RA中c-Kit + CPC扩增的细胞应答的关键介体。