Investigation of receptor-activated Ca^<2+>-permeable channels in smooth muscle cells

平滑肌细胞中受体激活的Ca^2-通透性通道的研究

• 批准号: 13670691
• 负责人: NAKAJIMA Toshiaki
• 金额: $ 1.6万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670691/
• 关键词: Smooth muscle; Ca^<2+> permeable channel; Transient receptor potential; endothelin-1; Ca^<2+>-ion; Non-selective cation channel; smooth muscle; Patch-clany; nonselective cation channel; Transient receptor potential; Endothelin-1; Intracellular

The contractile agonists such as endothelin-1 and vasopressin increase Ca^<2+> influx via several receptor-activated Ca^<2+> channels (Ca^<2+>-release-activated Ca^<2+> channel (CRAC) and Ca^<2+> permeable nonselective cation channels (I_<CAT>)). The analysis of RT-PCR showed the expression of transient receptor potential (TRP1,2,4) and TRP6. The latter may be related to I_<CAT>, and the former may be related to CRAC. Diacylglycerol produced from the activation of PLC, but not IP_3 and protein kinase C, may be involved in the activation of I_<CAT>. Similar results were obtained in human bronchial smooth muscle cells (Am J Respir Cell Mol Biol, 2000 ; 2002). In addition, we have reported that I_<CAT> plays an important role in forming membrane potential in rabbit coronary arterial cells, and lysophosphatidylcholine (LPC) further activated I_<CAT>. Thus, it is likely that I_<CAT> may play a role in regulating smooth muscle tone under the pathophysiological conditions.

收缩激动剂如内皮素-1和加压素通过几种受体激活的Ca^2+通道（Ca^2+释放激活的Ca ^2+通道（CRAC）和Ca^2+可渗透的非选择性阳离子通道（I））增加Ca^2+内流<CAT>。RT-PCR分析显示瞬时受体电位（TRP 1、2、4）和TRP 6的表达。后者可能与I有关<CAT>，前者可能与CRAC有关。PLC激活产生的甘油二酯可能参与了I_2的激活，而IP_3和蛋白激酶C则不参与<CAT>。在人支气管平滑肌细胞中获得了类似的结果（Am J Respir Cell Mol Biol，2000 ; 2002）。此外，我们还报道了I_2<CAT>在兔冠状动脉细胞膜电位形成中起重要作用，溶血磷脂酰胆碱（LPC）进一步激活<CAT>I_2。因此，<CAT>在病理生理条件下，I_2可能在调节平滑肌张力中起作用。

项目成果

Y.Okuda et al.: "Acute gliclazide administration enhances glucose and ketone body utilization in the perfused hind limb of normal and streptozotocin-diabetic rats"Life Sciences. 71. 647-654 (2002)

Y.Okuda 等人：“急性格列齐特给药可增强正常大鼠和链脲佐菌素糖尿病大鼠灌注后肢的葡萄糖和酮体利用”生命科学。

K.Terasawa, T.Nakajima et al.: "Nonselective cation currents regulate membrane potential of rabbit coronary arterial cell : Modulation by lysophosphatidylcholine"Circulation. 106. 3111-3119 (2002)

K.Terasawa、T.Nakajima 等人：“非选择性阳离子电流调节兔冠状动脉细胞的膜电位：溶血磷脂酰胆碱的调节”循环。

K Terasawa, T Nakgawa et al.: "Nonselective cation currents regulate membrane potential of rabbit coronary arterial cell: modulation by lysophosphatidylcholine"Circulation. 106. 3111-3119 (2002)

K Terasawa、T Nakkawa 等人：“非选择性阳离子电流调节兔冠状动脉细胞的膜电位：溶血磷脂酰胆碱的调节”循环。

T.Kawada et al.: "Rescue of hereditary form of dilated cardiomyopathy by rAAV-mediated somatic gene therapy"Proc. Natl Acad Sci USA. 99. 901-906 (2002)

T.Kawada 等人：“通过 rAAV 介导的体细胞基因疗法挽救遗传性扩张型心肌病”Proc。

Y.Okuda: "Acute gliceagide administration enhances glucose and ketone body utilization in the perfused normal and streptozotocin dialectic rat hind lim"Lfe Science. (in press). (2002)

Y.Okuda：“在正常灌注和链脲佐菌素方证的大鼠后肢中，急性服用格列宁可增强葡萄糖和酮体的利用”Lfe Science。