1990 Fiscal Year Final Research Report Summary
Expression Mechanism of Fibrinogen Receptor Function in Human Platelets.
| Project/Area Number |
01570360
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
内科学一般
|
|---|
| Research Institution | Hiroshima University |
|---|
Principal Investigator |
FUJIMURA King Research Institute for Nuclear Medicine and Biology, Hiroshima Univ., Associate Professor, 原爆放射能医学研究所, 助教授 (80034114)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KURAMOTO Atsushi Research Institute for Nuclear Medicine and Biology, Hiroshima Univ., Professor, 原爆放射能医学研究所, 教授 (50034070)
FUJIMOTO Tetsuro Health Service Center, Hiroshima Univ., Research Associate, 保健管理センター, 助手 (00221549)
KIMURA Akiro Faculty of Medicine, Hiroshima Univ., Assistant Professor, 講師 (70127645)
|
|---|
| Project Period (FY) |
1989 – 1990
|
| Keywords | Platelet membrane glycoprotein / GPIIb-IIIa complex / Fibrinogen receptor / Ca^<2+> channel / Protein conformation / liposome / Planar lipid bilayer / Fluorescence spectrum |
|---|
| Research Abstract |
Platelet membrane glycoprotein GPIIb and IIIa form a Ca^<2+> dependent heterodimer complex and this complex function as a fibrinogen receptor. The GPIIb and IIIa are present as complex in unstimulated platelet membrane surface but have not receptor function without stimulation. The expression mechanism of fibrinogen receptor function of GPIIb-IIIa complex during platelet activation is unknown. To determine whether the GPIIb-IIIa complex change the conformation at various Ca^<2+> concentrations or not, the conformation of GPIIb-IIIa complex was examined by fluorescense spectrophotometer and circular dichroism. The purified GPIIb-IIIa complex from human platelet membrane was composed of the alpha^*-herix and beta sheet structure did not change in various Ca^<2+> concentrations by circular dichroism analysis. The tryptophan fluorescence of the GPIIb-IIIa complex was measured with excitation at 280 nm and emission from 300 to 400 nm. The emission peak shift from short to long wave length w
… More
ith Ca^<2+> concentration dependently. This finding suggest that the areas in GPIIb-IIIa complex molecule which close to tryptophan change the conformation from hydrophobic state to hydrophilic state with Ca^<2+> concentration dependently. But the relative quantum yield of tryptophan of GPIIb-IIIa complex did not change within the physiological Ca^<2+> concentrations. These spectrophotometorical analysis showed the intracellular Ca^<2+> concentration (10^<-6>-10^<-8>M) did not induced the conformational change of GPIIb-IIIa complex directly. Next study was planned to determine the Ca^<2+> channel activity present or not in GPIIb-IIIa complex. The liposome membrane which was inserted purified GPIIb-IIIa complex coninflux Ca^<2+> but the dissociated GPII, IIIa inserted liposom membrane did not. The activated platelet membrane showed the voltage independent Ca^<2+> channel activity by a planar phospholipid bilayer technique. This channel activity was disappeared in EGTA, anti GPIIb-IIIa Moab or RGDS treated membranes. The purified GPIIb-IIIa complex inserted liposomes were incorporated into planar phospholipid dilayer and the Ca^<2+> channel current was measured. A voltage independent single channel current was detected, and which channel conductance was 10 PS. It was concluded that the purified GPIIb-IIIa complex can act as a divalent cation-permeable channel. Less
|
Research Products
(22 results)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Publications] Fujimura, K., et al: "Physicochemical properties of GPVfl level in plasma." Platelet 1990 「Platelet and Arteriosclerosis」 (eds by Ashino-ko Platelet Conference Yamazaki, H., Aoki, N., Hidaka, H., Kuramoto, A., Okuma, M.). 108-113 (1990)
Description
「研究成果報告書概要(欧文)」より
