1998 Fiscal Year Annual Research Report

エンドセリンとその受容体の薬理学の基礎

Research Project

Project/Area Number	09044289
Research Institution	National Cardiovascular Center Research Institute
Principal Investigator	眞崎知生国立循環器病センター研究所, 所長 (60009991)
Co-Investigator(Kenkyū-buntansha)	沢村達也国立循環器病センター研究所, バイオサイエンス部, 室長 (30243033) VANHOUTTE P. Institute de Recherches Internationales, 副所長 VANE J. St. Bartholomew's Hospital Medical Colleg, 教授
Keywords	エンドセリン / エンドセリン受容体 / エンドセリン受容体拮抗薬 / エンドセリン変換酵素 / 国際薬理学連合受容体委員会 / 国際エンドセリン会議
Research Abstract	本研究計画の目的は、世界のエンドセリン研究を進展させ、その方向性を定めることである。特に、国際薬理学連合受容体命名委員会とその小委員会の活動を通じ、また個人レベル、学会レベルの活動を通じて情報を収集、2年毎に開催される国際エンドセリン会議に集約させることを行った。本年度は、ドイツ・ミュンヘンにおける国際会議と委員会、イタリア・パドバ、オーストラリア・ケアンズ、米国・ダラス、米国・ロスアンジェルスにおける国際会議に出席、エンドセリン関連情報の収集、討論を行った。さらに過去7年間にわたるこれらの活動から、国際薬理学連合受容体命名委員会の統括として概要を本年度出版した。そのエンドセリン受容体の章は、本研究計画の集約である。エンドセリン研究の現状に関しては、心血管系については生理的にはエンドセリンが内皮から分泌された後、内皮自身に働き弛緩因子を分泌させる作用の方が平滑筋に働いて収縮を起こさせるより優位であるようである。病的状態では収縮作用の方が強く出るようである。特に異所性に産生されるエンドセリンが臨床症状を増悪させる。様々な今後の問題があるが、エンドセリン拮抗薬をどのように使うかが多くの研究者の当面の問題である。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] K.Ono et al.: "Desensitization of 1:T_A endothelin receptor-mediated negative chronotropic response in right atria-specics difference and intrancellular mechanisms" Br.J.Pharmacol.125. 787-797 (1998)
[Publications] T.Kido et al.: "The processing pathway of endothelin-1 production." J.Cardiovas.Pharmacol.31 Suppl.1. S13-S15 (1998)
[Publications] Y.Okamoto et al.: "Cysteine residues in the carboxyl terminal domain of the endothelin-B receptor are required for coupling with G-proteins." J.Cardiovas.Pharmacol.31 Suppl.1. S230-S232 (1998)
[Publications] M.Okazawa et al.: "Endothelin-induced apoptosis of A375 human melanoma cells" J.Biol.Chem.273. 12584-12592 (1998)
[Publications] H.Tanaka et al.: "Novel mutations of the endothelin B receptor gene in patients with hirschsprung's disease and their characterization" J.Biol.Chem.273. 11378-11383 (1998)
[Publications] B.Nicholson et al.: "Increased Cat3-mediated cationic amino acid transport functionally compensates in cat1 knockout cell lines" J.Biol.Chem.273. 14663-14666 (1998)
[Publications] H.Hasegawa et al.: "Purification of a novel endothelin-converting cnzyme specific for big endothelin-3" FEBS Letters. 428. 304-308 (1998)
[Publications] K.Oka et al.: "Lectin-like oxidized low-density lipoprotein receptor 1 mediates phagocytosis of aged/apoptotic cells in endothelial cells" Proc.Natl.Acad Sci.USA. 95. 9535-9540 (1998)
[Publications] Y.Iwamuro et al.: "Activation of two types of Ca^<1 >-permeable nonselective cation channel by endothelin-1 in A7r5 cells" Br.J.Pharmacol.124. 1541-1549 (1998)
[Publications] N.Kume et al.: "Inducible expression of Lectin-like oxidized LDL receptor-1 in vascular endothelial cells" Circ.Res.83. 322-327 (1998)
[Publications] T.Murase et al.: "Fluid shear stress transcriptionally induces Lectin-like oxidezed LDL receptor-1 in vascular endothelial cells" Circ.Res.83. 328-333 (1998)
[Publications] X.F.Zhang et al.: "Role of nonselective cation channels as Ca^<2+> entry pathway in endothelin-1-induced contraction and their suppression by nitric oxide" Eur.J.Pharmacol.352. 237-245 (1998)
[Publications] H.Hoshikawa et al.: "High affinity binding of oxidized LDL to mouse lectin-like oxidized LDL receptor(LOX-1)" Biochem.Biophys.Res.Commun.245. 841-846 (1998)
[Publications] N.Ninomiya et al.: "Paracrine endothelin signaling in the control of basal cell proliferation in guinea pig tracheal epithelium" J.Pharmacol.Exp.Ther.286. 469-480 (1998)
[Publications] K.Kikuta et al.: "High-affinity arginine transport of bovine aortic endothelial cells is impaired by lysophosphatidylcholine" Circ.Res.83. 1088-1096 (1998)
[Publications] Y.Iwamuro et al.: "Activation of three types of voltage-independent Ca^<2+>-entry channel in A7r5 cells by endothelin-1 as revealed by a novel Ca^<2+>-entry channel blocker LOE 908" Br.J.Pharmacol.,. (in press).
[Publications] T.Aoyama et al: "Structure and chromosomal assignment of human lectin-like oxidized LDL receptor-1(LOX-1)" Biochem.J.,. (in press).
[Publications] T.Inuri et al.: "Selective activation of excitation-contraction coupling pathways by ET_A and ET_B in tracheal smooth muscle" Br.J.Pharmacol.,. (in press).

1998 Fiscal Year Annual Research Report

エンドセリンとその受容体の薬理学の基礎

Principal Investigator

眞崎 知生 国立循環器病センター研究所, 所長 (60009991)

Research Products

[Publications] K.Ono et al.: "Desensitization of 1:T_A endothelin receptor-mediated negative chronotropic response in right atria-specics difference and intrancellular mechanisms" Br.J.Pharmacol.125. 787-797 (1998)

[Publications] T.Kido et al.: "The processing pathway of endothelin-1 production." J.Cardiovas.Pharmacol.31 Suppl.1. S13-S15 (1998)

[Publications] Y.Okamoto et al.: "Cysteine residues in the carboxyl terminal domain of the endothelin-B receptor are required for coupling with G-proteins." J.Cardiovas.Pharmacol.31 Suppl.1. S230-S232 (1998)

[Publications] M.Okazawa et al.: "Endothelin-induced apoptosis of A375 human melanoma cells" J.Biol.Chem.273. 12584-12592 (1998)

[Publications] H.Tanaka et al.: "Novel mutations of the endothelin B receptor gene in patients with hirschsprung's disease and their characterization" J.Biol.Chem.273. 11378-11383 (1998)

[Publications] B.Nicholson et al.: "Increased Cat3-mediated cationic amino acid transport functionally compensates in cat1 knockout cell lines" J.Biol.Chem.273. 14663-14666 (1998)

[Publications] H.Hasegawa et al.: "Purification of a novel endothelin-converting cnzyme specific for big endothelin-3" FEBS Letters. 428. 304-308 (1998)

[Publications] K.Oka et al.: "Lectin-like oxidized low-density lipoprotein receptor 1 mediates phagocytosis of aged/apoptotic cells in endothelial cells" Proc.Natl.Acad Sci.USA. 95. 9535-9540 (1998)

[Publications] Y.Iwamuro et al.: "Activation of two types of Ca^<1 >-permeable nonselective cation channel by endothelin-1 in A7r5 cells" Br.J.Pharmacol.124. 1541-1549 (1998)

[Publications] N.Kume et al.: "Inducible expression of Lectin-like oxidized LDL receptor-1 in vascular endothelial cells" Circ.Res.83. 322-327 (1998)

[Publications] T.Murase et al.: "Fluid shear stress transcriptionally induces Lectin-like oxidezed LDL receptor-1 in vascular endothelial cells" Circ.Res.83. 328-333 (1998)

[Publications] X.F.Zhang et al.: "Role of nonselective cation channels as Ca^<2+> entry pathway in endothelin-1-induced contraction and their suppression by nitric oxide" Eur.J.Pharmacol.352. 237-245 (1998)

[Publications] H.Hoshikawa et al.: "High affinity binding of oxidized LDL to mouse lectin-like oxidized LDL receptor(LOX-1)" Biochem.Biophys.Res.Commun.245. 841-846 (1998)

[Publications] N.Ninomiya et al.: "Paracrine endothelin signaling in the control of basal cell proliferation in guinea pig tracheal epithelium" J.Pharmacol.Exp.Ther.286. 469-480 (1998)

[Publications] K.Kikuta et al.: "High-affinity arginine transport of bovine aortic endothelial cells is impaired by lysophosphatidylcholine" Circ.Res.83. 1088-1096 (1998)

[Publications] Y.Iwamuro et al.: "Activation of three types of voltage-independent Ca^<2+>-entry channel in A7r5 cells by endothelin-1 as revealed by a novel Ca^<2+>-entry channel blocker LOE 908" Br.J.Pharmacol.,. (in press).

[Publications] T.Aoyama et al: "Structure and chromosomal assignment of human lectin-like oxidized LDL receptor-1(LOX-1)" Biochem.J.,. (in press).

[Publications] T.Inuri et al.: "Selective activation of excitation-contraction coupling pathways by ET_A and ET_B in tracheal smooth muscle" Br.J.Pharmacol.,. (in press).

眞崎知生国立循環器病センター研究所, 所長 (60009991)