Restraint Stress Induces Connexin-43 Translocation via α-Adrenoceptors in Rat Heart
Restraint Stress Induces Connexin-43 Translocation via α-Adrenoceptors in Rat Heart
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DOI：
10.1253/circj.cj-10-0529
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发表时间：
2010-12-01
影响因子：
3.3
通讯作者：
Yoshida, Ken-ichi
中科院分区：
文献类型：
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作者：
Unuma, Kana;Shintani-Ishida, Kaori;Yoshida, Ken-ichi
背景：固定化（IMO）会给动物和人类带来情绪压力。最近有报道称，大鼠的IMO诱导连接蛋白43 （Cx43）易位至间隙连接（GJs），并通过GJ抑制减弱心律失常发生，同时也显示了Cx43在缺血心脏中的易位。很少有报道显示肾上腺素受体在心肌细胞中对Cx43上调的贡献，但肾上腺素受体和缺血在心肌组织中Cx43易位的参与仍然是未知的。方法与结果：雄性Sprague-Dawley大鼠经IMO后，采用western blotting检测Cx43在脑室的分布，IMO诱导Cx43向富含gj的膜部分易位，在60 min时达到峰值。（α 1）-肾上腺素受体阻滞剂吡唑嗪（1mg /kg， PO）和布纳唑嗪（4mg /kg， PO）预处理可抑制imo诱导的Cx43易位，但β(1)-受体阻滞剂美托洛尔（10mg /kg， IP）或β(1+2)受体阻滞剂普萘洛尔（1mg /kg， PO）预处理均不能抑制Cx43易位。一氧化氮、供体硝酸异山梨酯(100 μ g kg（-1) min(-1)， IV）可能通过交感神经抑制抑制了易位。缺氧诱导因子-1 α未被IMO重新分配。-受体阻滞剂对IMO诱导的室性早搏有抑制作用，而α受体阻滞剂没有作用。结论：Cx43易位到gj富集部分是通过α(1)-肾上腺素能受体途径发生的，与缺血无关。-肾上腺素能受体途径参与了IMO中室性早搏的诱导。（Circ J 2010; 74: 2693-2701）
Background: Immobilization (IMO) confers emotional stress in animals and humans. It was recently reported that IMO in rats induced translocation of connexin-43 (Cx43) to gap junctions (GJs) and attenuated arrhythmogenesis with GJ inhibition, and Cx43 translocation in the ischemic heart was also shown. Few reports show the contribution of adrenoceptors to Cx43 upregulation in cardiomyocytes, but the involvement of adrenoceptors and ischemia in Cx43 translocation in IMO remains elusive.Methods and Results: Male Sprague-Dawley rats underwent IMO and the ventricular distribution of Cx43 was examined by western blotting IMO induced translocation of Cx43 to the GJ-enriched membrane fraction, with a peak at 60 min. The IMO-induced Cx43 translocation was inhibited by pretreatment with the (alpha 1)-adrenoceptor blockers, prazosin (1 mg/kg, PO) and bunazosin (4 mg/kg, PO), but not with either the beta(1)-blocker, metoprolol (10 mg/kg, IP), or the beta(1+2)-blocker, propranolol (1 mg/kg, PO). The translocation was inhibited by the nitric oxide, donor isosorbide dinitrate (100 mu g kg(-1) min(-1), IV), possibly through sympathetic inhibition. Hypoxia inducible factor-1 alpha was not redistributed by IMO. The beta-blockers, but not the alpha-blockers, inhibited the premature ventricular contractions (PVCs) induced by IMO.Conclusions: Translocation of Cx43 to the GJ-enriched fraction occurs via the alpha(1)-adrenoceptor pathway, independently of ischemia. The beta-adrenoceptor pathway contributes to the inducing of PVCs in IMO. (Circ J 2010; 74: 2693-2701)