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Please use this identifier to cite or link to this item:
http://140.112.115.32:8080/ir/handle/987654321/2769
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| Title: | Characteristics of endogenous γ-aminobutyric acid (GABA) in human platelets: functional studies of a novel collagen glycoprotein VI inhibitor |
| Authors: | 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 |
| Contributors: | 視光學系 |
| Keywords: | γ-Aminobutyric acid;Collagen;Convulxin;Glycoprotein VI antagonist;Platelet activation |
| Date: | 2014-06-01 |
| Issue Date: | 2025-08-01 15:07:00 (UTC+8) |
| Abstract: | 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. |
| Relation: | Journal of Molecular Medicine, 92(6), 603-614. https://doi.org/10.1007/s00109-014-1140-7 |
| Appears in Collections: | [視光學系] 期刊論文
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