Urotensin II promotes vagal-mediated bradycardia by activating cardiac-projecting parasympathetic neurons of nucleus ambiguus.
Urotensin II promotes vagal-mediated bradycardia by activating cardiac-projecting parasympathetic neurons of nucleus ambiguus.
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DOI：
10.1111/jnc.12679
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发表时间：
2014-05
影响因子：
4.7
通讯作者：
Brailoiu E
中科院分区：
文献类型：
--
作者：
Brailoiu GC;Deliu E;Rabinowitz JE;Tilley DG;Koch WJ;Brailoiu E
尿紧张素II （U-II）是一种调节中枢和外周部位心血管功能的环状非肽。U-II歧义核是控制心脏张力的关键部位，尽管U-II及其受体在这一水平上得到了鉴定，但其功能作用尚未确定。我们在这里报道，U-II通过两种途径在歧义核逆行标记的心脏迷走神经细胞中产生细胞质内Ca2+浓度的增加：(i) Ca2+通过肌醇1,4,5-三磷酸受体从内质网释放；（ii） Ca2+通过P/ q型Ca2+通道内流。此外，U-II使培养的心脏副交感神经细胞去极化。将浓度增加的U-II微注射到模糊核中，会引起有意识大鼠的剂量依赖性心动过缓，表明体内激活了控制心率的胆碱能通路。体外和体内作用均被尿紧张素受体拮抗剂urantide所消除。我们的研究结果表明，除了之前报道的交感神经流出增加外，U-II激活了模棱两可核的心脏迷走神经，这可能有助于心脏保护。
Urotensin II (U-II) is a cyclic undecapeptide that regulates cardiovascular function at central and peripheral sites. The functional role of U-II nucleus ambiguus, a key site controlling cardiac tone, has not been established, despite the identification of U-II and its receptor at this level. We report here that U-II produces an increase in cytosolic Ca2+ concentration in retrogradely labeled cardiac vagal neurons of nucleus ambiguus via two pathways: (i) Ca2+ release from the endoplasmic reticulum via inositol 1,4,5-trisphosphate receptor; and (ii) Ca2+ influx through P/Q-type Ca2+ channels. In addition, U-II depolarizes cultured cardiac parasympathetic neurons. Microinjection of increasing concentrations of U-II into nucleus ambiguus elicits dose-dependent bradycardia in conscious rats, indicating the in vivo activation of the cholinergic pathway controlling the heart rate. Both the in vitro and in vivo effects were abolished by the urotensin receptor antagonist, urantide. Our findings suggest that, in addition, to the previously reported increase in sympathetic outflow, U-II activates cardiac vagal neurons of nucleus ambiguus, which may contribute to cardioprotection.
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影响因子：
4.7
作者：
Brailoiu GC;Deliu E;Tica AA;Rabinowitz JE;Tilley DG;Benamar K;Koch WJ;Brailoiu E
通讯作者：
Brailoiu E
影响因子：
2.5
作者：
Dun, SL;Brailoiu, GC;Dun, NJ
通讯作者：
Dun, NJ
影响因子：
3.3
作者：
Lewinter, R. D.;Scherrer, G.;Basbauma, A. I.
通讯作者：
Basbauma, A. I.
影响因子：
4.7
作者：
Brailoiu GC;Deliu E;Tica AA;Chitravanshi VC;Brailoiu E
通讯作者：
Brailoiu E
影响因子：
7.3
作者：
Camarda, V;Spagnol, M;Calò, G
通讯作者：
Calò, G