1991 Fiscal Year Annual Research Report

心筋興奮・伝導の細胞内調節機構

Research Project

Project/Area Number	03253102
Research Institution	The University of Tokyo
Principal Investigator	杉本恒明東京大学, 医学部(病), 教授 (60019883)
Co-Investigator(Kenkyū-buntansha)	堅田利明東京工業大学, 生命理工学部, 教授 (10088859) 今井昭一新潟大学, 医学部, 教授 (60013869) 飯島俊彦秋田大学, 医学部, 教授 (30004724) 遠藤政夫山形大学, 医学部, 教授 (40004668) 中谷晴昭北海道大学, 医学部, 助教授 (60113594)
Keywords	G蛋白 / ムスカリン性Kチャネル / GTP / NDPキナ-ゼ / α受容体 / β受容体 / 蛋白燐酸化酵素 / ミトコンドリアDNA遺伝子
Research Abstract	1)単離心筋細胞の細胞内潅流を行いつつ,パッチ電極法により膜電流を記録解析することにより,アラキドン酸代謝系がI・K_<ACh>チャネルを活性調節すること,これが血小板活性化因子によっても活性化されることを示し,新しい情報伝達系を提示した(杉本)。 2)細胞膜を介する情報伝達系において,受容体,G蛋白,効果器系分子間の相互作用を制御する,新しいタイプの細胞内因子を中枢神経系に見出した(堅田)。本情報伝達系において,Cキナ-ゼ系やAキナ-ゼ系が,cーmycやcーfos遺伝子の発現を促進することを見出した。また,ras p21GAP以外にras p21などのGDP/GTP交換反応を調節する活性制御蛋白を精製している(貝淵)。 3)α受容体サブタイプ選択的拮抗薬を用いて,収縮性調節とP1代謝回転とは強い関連性を持つことを明らかにした(遠藤)。β受容体刺激時にはα受容体刺激時とは反対に細胞内pHが低下し,これはNaーK交換系を介さないことが見られた(中谷)。β受容体刺激時の,IcaとIkに対する作用の相違が明らかにされ,その細胞内情報伝達機構の差異が検討されている(飯島)。Cyclic GMP/Gーkinaseによって燐酸化されCa^<2+>ーATPaseと考えられてきた蛋白が,実は別の物であることを証明した(今井)。 4)細胞内代謝産物ないしはoxidative stressの心筋細胞Kチャネルに対する作用,ATP感受性Kチャネルの病態生理学的役割が示された(中谷)。 5)ミトコンドリア塩基配列を迅速に解析する体制を整備し,30例以上のミトコンドリアDNA病患者に於ける遺伝子変異を報告した。また,酸化的DNA障害の程度と変異ならびに欠失等との間に正の相関があることを示した(小沢)。

Research Products
(12 results)

All Other

All Publications (12 results)

[Publications] Ito,H.: "On the mechanism of basal and agonist-induced activation of the G protein-gated muscarinic K channel in atrial myocytes of guineapit heart." J.Gen.Physiol.
[Publications] Nakaya,H.: "Effects of ATP-sensitive K+ channel blockers on the action potential chortening in hypoxic and ischaemic myocardium." Brit.J.Pharmacol.101. 1019-1026 (1991)
[Publications] Endoh,M.: "Myocardial alphal-adrenoceptors medicate positive inotropic effect and changes in phosphatidylinositol metabolism." Circulation Res.68. 1179-1190 (1991)
[Publications] Iijima,T.: "Differential modulation by beta adrenoceptors of the inward calcium and the delayed rectifier potassium current in single ventricular cells of the guinea pig heart." J.Pharmacol.Exp.Ther.254. 142-146 (1990)
[Publications] Yoshida,Y.: "Cyclic GMP-dependent protein kinase stimulates the plasma membrane Ca2+-pump ATPase of vascular smooth muscle via phosphorylation of a 240-kDa protein." J.Biol.Chem.
[Publications] Iiri,T.: "Modification of the function of pertussis toxin-substrate.GTP-binding protein by cholera toxin-catalysed ADP-ribosylation." J.Biol.Chem.
[Publications] Ozawa,T.: "Distinct clustering of point mutations in mitochondrial DNA amond patinets with mitochondrial encephalomyopathies and with Parkinson's disease." Biochem.Biophys.Res.Commun.176. 938-946 (1991)
[Publications] Mizuno,T.: "A stimulatory GDP/Gtp exchange protein for smg p21 is active on the porst-translationally processed form of c-Ki-ras p21 and rhoA p21." Proc.Natl.Acad.Sci.88. 6442-6446 (1991)
[Publications] Kaibuchi,K.: "Molecular cloning and characterization of the stimulatory GDP/GTP protein (GDS) for smg p21s,ras p21-like small GTP-binding proteins." Mol.Cell Biol.11. 2873-2880 (1991)
[Publications] Fujioka,H.: "Transforming and c-fos promoter/enhancer stimulating acitivities of a stimulatory GDP/GTP exchange protein for small GTP-binding proteins." J.Biol.Chem.
[Publications] Tanaka,M.: "Mitochondrial tRNA mutation in fatal infatile cardiomyopathy." Lancet. 336. 1452 (1990)
[Publications] Maehama,t.: "Identification of a botulinum C3-like enzyme in bovine brain that catalyzes ADP-ribosylation of GTP-binding proteins." J.Biol.Chem.266. 10062-10065 (1991)

1991 Fiscal Year Annual Research Report

心筋興奮・伝導の細胞内調節機構

Principal Investigator

杉本 恒明 東京大学, 医学部(病), 教授 (60019883)

Research Products

[Publications] Ito,H.: "On the mechanism of basal and agonist-induced activation of the G protein-gated muscarinic K channel in atrial myocytes of guineapit heart." J.Gen.Physiol.

[Publications] Nakaya,H.: "Effects of ATP-sensitive K+ channel blockers on the action potential chortening in hypoxic and ischaemic myocardium." Brit.J.Pharmacol.101. 1019-1026 (1991)

[Publications] Endoh,M.: "Myocardial alphal-adrenoceptors medicate positive inotropic effect and changes in phosphatidylinositol metabolism." Circulation Res.68. 1179-1190 (1991)

[Publications] Iijima,T.: "Differential modulation by beta adrenoceptors of the inward calcium and the delayed rectifier potassium current in single ventricular cells of the guinea pig heart." J.Pharmacol.Exp.Ther.254. 142-146 (1990)

[Publications] Yoshida,Y.: "Cyclic GMP-dependent protein kinase stimulates the plasma membrane Ca2+-pump ATPase of vascular smooth muscle via phosphorylation of a 240-kDa protein." J.Biol.Chem.

[Publications] Iiri,T.: "Modification of the function of pertussis toxin-substrate.GTP-binding protein by cholera toxin-catalysed ADP-ribosylation." J.Biol.Chem.

[Publications] Ozawa,T.: "Distinct clustering of point mutations in mitochondrial DNA amond patinets with mitochondrial encephalomyopathies and with Parkinson's disease." Biochem.Biophys.Res.Commun.176. 938-946 (1991)

[Publications] Mizuno,T.: "A stimulatory GDP/Gtp exchange protein for smg p21 is active on the porst-translationally processed form of c-Ki-ras p21 and rhoA p21." Proc.Natl.Acad.Sci.88. 6442-6446 (1991)

[Publications] Kaibuchi,K.: "Molecular cloning and characterization of the stimulatory GDP/GTP protein (GDS) for smg p21s,ras p21-like small GTP-binding proteins." Mol.Cell Biol.11. 2873-2880 (1991)

[Publications] Fujioka,H.: "Transforming and c-fos promoter/enhancer stimulating acitivities of a stimulatory GDP/GTP exchange protein for small GTP-binding proteins." J.Biol.Chem.

[Publications] Tanaka,M.: "Mitochondrial tRNA mutation in fatal infatile cardiomyopathy." Lancet. 336. 1452 (1990)

[Publications] Maehama,t.: "Identification of a botulinum C3-like enzyme in bovine brain that catalyzes ADP-ribosylation of GTP-binding proteins." J.Biol.Chem.266. 10062-10065 (1991)

杉本恒明東京大学, 医学部(病), 教授 (60019883)