Urocortin 3 elevates cytosolic calcium in nucleus ambiguus neurons.
Urocortin 3 elevates cytosolic calcium in nucleus ambiguus neurons.
复制标题
DOI：
10.1111/j.1471-4159.2012.07869.x
复制
发表时间：
2012-09
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;Tica AA;Chitravanshi VC;Brailoiu E
Urocortin 3(也称为压力范围素)是促肾上腺皮质激素释放因子受体2(CRF2)的内源性配体。尽管CRF2以G偶联为主，但与其他G蛋白的混杂偶联也与该受体的激活有关。由于urocortin 3参与了下丘脑和延髓部位的心血管中枢调节，我们研究了它对心脏疑核迷走神经元的细胞效应，疑核是自主控制心率的关键区域。Urocortin 3(1 nM~1000 nM)可引起细胞内钙浓度浓度依赖性增加，该作用可被CRF2拮抗剂K41498阻断。在用urocortin 3连续两次治疗的情况下，urocortin 3诱导的第二个Ca~(2+)反应减少，表明受体脱敏。用百日咳毒素预处理和用U-73122抑制磷脂酶C可使Urocortin 3的作用消失。Urocortin 3通过电压门控型P/Q型通道激活钙内流，并激活内质网钙释放。Urocortin 3通过肌醇1，4，5三磷酸受体促进Ca~(2+)释放，而不是兰尼定受体。我们的结果表明，urocortin 3在疑核的迷走神经节前神经元上有一种新的钙动员作用，为该肽在副交感神经心脏调节中的作用提供了细胞机制。
Urocortin 3 (also known as stresscopin) is an endogenous ligand for the corticotropin-releasing factor receptor 2 (CRF2). Despite predominant Gs-coupling of CRF2, promiscuous coupling with other G proteins has been also associated with the activation of this receptor. As urocortin 3 has been involved in central cardiovascular regulation at hypothalamic and medullary sites, we examined its cellular effects on cardiac vagal neurons of nucleus ambiguus, a key area for the autonomic control of heart rate. Urocortin 3 (1 nM to 1000 nM) induced a concentration-dependent increase in cytosolic Ca2+ concentration that was blocked by the CRF2 antagonist K41498. In the case of two consecutive treatments with urocortin 3, the second urocortin 3-induced Ca2+ response was reduced, indicating receptor desensitization. The effect of urocortin 3 was abolished by pretreatment with pertussis toxin and by inhibition of phospolipase C with U-73122. Urocortin 3 activated a Ca2+ influx via voltage-gated P/Q-type channels as well as Ca2+ release from endoplasmic reticulum. Urocortin 3 promoted Ca2+ release via inositol 1,4,5 trisphosphate receptors but not ryanodine receptors. Our results indicate a novel Ca2+- mobilizing effect of urocortin 3 in vagal preganglionic neurons of nucleus ambiguus, providing a cellular mechanism for a previously reported role for this peptide in parasympathetic cardiac regulation.
登录
查看更多内容
影响因子：
--
作者：
Kostich, WA;Chen, AR;Largent, BL
通讯作者：
Largent, BL
影响因子：
4
作者：
Berridge, MJ
通讯作者：
Berridge, MJ
DOI：
10.1073/pnas.121165198
发表时间：
2001-06-19
影响因子：
11.1
作者：
Lewis, K;Li, C;Vale, WW
通讯作者：
Vale, WW
影响因子：
64.8
作者：
KATZ, A;WU, DQ;SIMON, MI
通讯作者：
SIMON, MI
DOI：
10.1073/pnas.92.4.1108
发表时间：
1995-02-14
影响因子：
11.1
作者：
KISHIMOTO, T;PEARSE, RV;ROSENFELD, MG
通讯作者：
ROSENFELD, MG