Characteristics of endogenous γ-aminobutyric acid (GABA) in human platelets: functional studies of a novel collagen glycoprotein VI inhibitor

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://140.112.115.32:8080/ir/handle/987654321/2769

题名:	Characteristics of endogenous γ-aminobutyric acid (GABA) in human platelets: functional studies of a novel collagen glycoprotein VI inhibitor
作者:	Kuan-Hung Lin;Wan-Jung Lu;Shwu-Huey Wang;Tsorng-Harn Fong;Duen-Suey Chou;Chao-Chien Chang;Nen-Chung Chang;Yung-Chen Chiang;Shih-Yi Huang;Joen-Rong Sheu
贡献者:	視光學系
关键词:	γ-Aminobutyric acid;Collagen;Convulxin;Glycoprotein VI antagonist;Platelet activation
日期:	2014-06-01
上传时间:	2025-08-01 15:07:00 (UTC+8)
摘要:	gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system, and it also appears in peripheral tissues. Platelets are anuclear blood cells that play a central role in hemostatic processes. Although platelets possess a GABA uptake system, the functional activity of GABA in platelets has remained unclear. We determined that GABA is abundantly distributed in the platelets at a concentration of approximately 1.03 ng/106 cells. GABA (0.5 μM) specifically inhibited collagen-induced platelet activation accompanied by [Ca2+]i mobilization, phospholipase Cγ2, protein kinase C, Akt phosphorylation, and hydroxyl radical formation. In addition, GABA interfered with fluorescein isothiocyanate–collagen binding to platelet membranes and produced a concentration-dependent shift in the collagen concentration–response curve and a Schild plot slope of -0.96 ± 0.11, indicating competitive inhibition. Platelet activation induced by convulxin, a glycoprotein VI agonist, was inhibited by GABA, whereas activation induced by the integrin α2β1 agonist, aggretin, was not. Immunoprecipitation and surface plasmon resonance revealed that GABA binds directly to glycoprotein VI in human platelets with equilibrium dissociation (binding) constant (K D) of 41.4 nM. The closure time of whole blood and the occlusion time of platelet plug formation were significantly prolonged by GABA in vivo. In this study, GABA is a specific inhibitor of collagen glycoprotein VI and may be involved in an endogenous negative feedback mechanism for platelet activation. Thus, GABA may represent a potential target for the development of novel interventions for the treatment of cardiovascular diseases associated with platelet activation, such as stroke and myocardial infarction.
關聯:	Journal of Molecular Medicine, 92(6), 603-614. https://doi.org/10.1007/s00109-014-1140-7
显示于类别:	[視光學系] 期刊論文

文件中的档案:

档案	大小	格式	浏览次数
index.html	0Kb	HTML	27	检视/开启

在MMUIR中所有的数据项都受到原著作权保护.

数据加载中.....