1991 Fiscal Year Annual Research Report

心筋αー受容体情報伝達機構の分子薬理学的解析

Research Project

Project/Area Number	03454142
Research Institution	Yamagata University
Principal Investigator	遠藤政夫山形大学, 医学部, 教授 (40004668)
Co-Investigator(Kenkyū-buntansha)	石幡明山形大学, 医学部, 助手 (40232326)
Keywords	心筋α受容体 / 陽性変力作用 / イノシト-ル燐脂質代謝促進 / α_<1A>受容体 / α_<1B>受容体 / エンドセリン / クロルエチルクロニジン / ホルボ-ルエステル
Research Abstract	1.心筋α受容体刺激とエンドセリン受容体刺激の類似性:心筋α受容体は神経伝達物質および流血中のカテコ-ルアミンによって刺激されるのに対して,エンドセリン(ET)受容体は病態生理学的な意義を持つことが推定されている。すなわちETは血管内皮細胞から遊離されてその特異的受容体に結合することにより心筋および血管平滑筋細胞の病態生理学的細胞内情報伝達をトリガ-する。本研究において心筋α受容体とET受容体刺激は多くの類似性を持ち,その共通の情報伝達系としてイノシト-ル燐脂質(PI)代謝促進による過程が重要であることを示唆する実験結果が得られた。両受容体刺激は以下の点で類似している。(1)陽性変力作用がPI代謝促進に伴われている。(2)Cキナ-ゼ活性化作用を持つホルボ-ルエステル(phorbol 12,13ーdibutyrate)は両受容体を介する陽性変力作用とPI代謝促進を同時に遮断する。(3)両受容体を介する収縮張力修飾は,収縮持続時間の延長に伴われて起こり,その最大反応はイソプロテレノ-ルの約60%で,両者の反応は一方の最大反応のレベルまでのみ相加的である。(4)両受容体を介する収縮張力増強はともに収縮タンパクのカルシウム感受性増強に伴われている(エンドセリンに関しては米国の研究グル-プのデ-タ)などの点である。今後さらにPI代謝促進作用を持つ他の受容体系刺激効果との類似性の比較から心筋収縮調節におけるPI代謝の意義を追求する予定である。 2.心筋α受容体のサブタイプについて:心筋α受容体(R)はα_1サブタイプに属する。α_1ーRはさらにα_<1A>ーRとα_<1B>ーRに亜分類し得る。α_<1A>ーRはL型Caチャンネルに共役しているのに対して,α_<1B>ーRはGTP結合タンパクGqを介してPI代謝促進に共役している。α_<1B>ーR選択性を持つchlorethylclonidine(CEC)の抑制効果からも心筋α_1ーRの約70%はα_<1B>ーRであることを明らかにした。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] 遠藤政夫: "Inotropic effects of endothelin on mammalian ventricular contractility." Basic Research in Cardiology. 86(S1). 173-178 (1991)
[Publications] 遠藤政夫: "Myocardial α_1ーadrenoceptors mediate positive inotropic effect and changes in phosphatidylinositol metabolism: species differences in receptor distribution and the intracellular coupling process in mammalian ventricular myocardium." Circulation Research. 68. 1179-1190 (1991)
[Publications] 遠藤政夫: "Myocardial αーadrenoceptors: multiplicity of subcellular coupling processes." Asia Pacific Journal of Pharmacology. 6. 171-186 (1991)
[Publications] 高梨正博: "Potent inhibitory action of chlorethylclonidine on the positive inotropic effect and phosphoinositide hydrolysis mediated via myocardial alpha_1ーadrenoceptors in the rabbit ventricular myocardium." NaunynーSchmiedeberg's Arch.Pharmacol.343. 669-673 (1991)
[Publications] 高梨正博: "Characterization of the positive inotropic effect of endothelin on mammalian ventricular myocardium." American Journal of Physiology. 261. H611-H619 (1991)
[Publications] 遠藤政夫: "Differential inhibitory action of phorbolー12,13ーdibutyrate on the positive inotropic effect of endothelinー1 and Bay K 8644 in the isolated rabbit papillary muscle." Journal of Cardiovasculax Pharmacology. 17(S.7). S165-S168 (1991)
[Publications] 遠藤政夫: "Signal transduction of myocardial α_1ーadrenoceptors: regulation of ion channels,intracellular calcium,and force of contractionーa review." Journal of Applied Cardiology. 6. 379-399 (1991)
[Publications] 遠藤政夫: "Physiological and pathophysiological modulation of calcium signaling in myocardial cells." Japanese Circulation Journal. 55. 1108-1117 (1991)
[Publications] 石幡明: "Subcellular mechainism of desensitization of the ATPーinduced Ca^<2+>mobilization in human umbilical vein endothelial cells: role of intracellular Ca^<2+> stores." Life Sciences. 48. 583-591 (1991)
[Publications] 遠藤政夫: "Phosphoinositide hydrolysis and positive inotropic effect induced by endothelin in the rabbit ventricular muscle." Physiologist. 34. 110 (1991)
[Publications] 遠藤政夫: "Selective inhibition by stanrosporine and phorbol ester of the positive inotropic effect mediated by αー1 adrenergic receptors." Physiologist. 34. 110 (1991)
[Publications] 石幡明: "Influence of aging on the contractile response to endothelin of rat thoracic aorta." European Journal of Pharmacology. 200. 199-201 (1991)
[Publications] 遠藤政夫: "Role of alpha_<1A> adrenoceptor subtype in production of the positive inotropic effect mediated via myocardial aopha_1 adrenoceptors in the rabbit papillary muscle: influence of selective alpha_<1A> subtype antagonists WB 4101 and 5ーmethylurapidil." NaunynーSchmiede berg's Arch.Pharmacol.(1992)
[Publications] 遠藤政夫: "α,β受容体の生化学・薬理学" 綜合臨牀. 40. 2442-2449 (1991)
[Publications] 遠藤政夫: "心筋細胞内Ca動態と心筋収縮" 病態生理. 10. 430-436 (1991)
[Publications] 遠藤政夫: "心筋のαおよびβ受容体の意義" 臨床科学. 27. 334-339 (1991)

1991 Fiscal Year Annual Research Report

心筋αー受容体情報伝達機構の分子薬理学的解析

Principal Investigator

遠藤 政夫 山形大学, 医学部, 教授 (40004668)

Research Products

[Publications] 遠藤 政夫: "Inotropic effects of endothelin on mammalian ventricular contractility." Basic Research in Cardiology. 86(S1). 173-178 (1991)

[Publications] 遠藤 政夫: "Myocardial αーadrenoceptors: multiplicity of subcellular coupling processes." Asia Pacific Journal of Pharmacology. 6. 171-186 (1991)

[Publications] 高梨 正博: "Potent inhibitory action of chlorethylclonidine on the positive inotropic effect and phosphoinositide hydrolysis mediated via myocardial alpha_1ーadrenoceptors in the rabbit ventricular myocardium." NaunynーSchmiedeberg's Arch.Pharmacol.343. 669-673 (1991)

[Publications] 高梨 正博: "Characterization of the positive inotropic effect of endothelin on mammalian ventricular myocardium." American Journal of Physiology. 261. H611-H619 (1991)

[Publications] 遠藤 政夫: "Differential inhibitory action of phorbolー12,13ーdibutyrate on the positive inotropic effect of endothelinー1 and Bay K 8644 in the isolated rabbit papillary muscle." Journal of Cardiovasculax Pharmacology. 17(S.7). S165-S168 (1991)

[Publications] 遠藤 政夫: "Signal transduction of myocardial α_1ーadrenoceptors: regulation of ion channels,intracellular calcium,and force of contractionーa review." Journal of Applied Cardiology. 6. 379-399 (1991)

[Publications] 遠藤 政夫: "Physiological and pathophysiological modulation of calcium signaling in myocardial cells." Japanese Circulation Journal. 55. 1108-1117 (1991)

[Publications] 石幡 明: "Subcellular mechainism of desensitization of the ATPーinduced Ca^<2+>mobilization in human umbilical vein endothelial cells: role of intracellular Ca^<2+> stores." Life Sciences. 48. 583-591 (1991)

[Publications] 遠藤 政夫: "Phosphoinositide hydrolysis and positive inotropic effect induced by endothelin in the rabbit ventricular muscle." Physiologist. 34. 110 (1991)

[Publications] 遠藤 政夫: "Selective inhibition by stanrosporine and phorbol ester of the positive inotropic effect mediated by αー1 adrenergic receptors." Physiologist. 34. 110 (1991)

[Publications] 石幡 明: "Influence of aging on the contractile response to endothelin of rat thoracic aorta." European Journal of Pharmacology. 200. 199-201 (1991)

[Publications] 遠藤 政夫: "α,β受容体の生化学・薬理学" 綜合臨牀. 40. 2442-2449 (1991)

[Publications] 遠藤 政夫: "心筋細胞内Ca動態と心筋収縮" 病態生理. 10. 430-436 (1991)

[Publications] 遠藤 政夫: "心筋のαおよびβ受容体の意義" 臨床科学. 27. 334-339 (1991)

遠藤政夫山形大学, 医学部, 教授 (40004668)

[Publications] 遠藤政夫: "Inotropic effects of endothelin on mammalian ventricular contractility." Basic Research in Cardiology. 86(S1). 173-178 (1991)

[Publications] 遠藤政夫: "Myocardial αーadrenoceptors: multiplicity of subcellular coupling processes." Asia Pacific Journal of Pharmacology. 6. 171-186 (1991)

[Publications] 高梨正博: "Potent inhibitory action of chlorethylclonidine on the positive inotropic effect and phosphoinositide hydrolysis mediated via myocardial alpha_1ーadrenoceptors in the rabbit ventricular myocardium." NaunynーSchmiedeberg's Arch.Pharmacol.343. 669-673 (1991)

[Publications] 高梨正博: "Characterization of the positive inotropic effect of endothelin on mammalian ventricular myocardium." American Journal of Physiology. 261. H611-H619 (1991)

[Publications] 遠藤政夫: "Differential inhibitory action of phorbolー12,13ーdibutyrate on the positive inotropic effect of endothelinー1 and Bay K 8644 in the isolated rabbit papillary muscle." Journal of Cardiovasculax Pharmacology. 17(S.7). S165-S168 (1991)

[Publications] 遠藤政夫: "Signal transduction of myocardial α_1ーadrenoceptors: regulation of ion channels,intracellular calcium,and force of contractionーa review." Journal of Applied Cardiology. 6. 379-399 (1991)

[Publications] 遠藤政夫: "Physiological and pathophysiological modulation of calcium signaling in myocardial cells." Japanese Circulation Journal. 55. 1108-1117 (1991)

[Publications] 石幡明: "Subcellular mechainism of desensitization of the ATPーinduced Ca^<2+>mobilization in human umbilical vein endothelial cells: role of intracellular Ca^<2+> stores." Life Sciences. 48. 583-591 (1991)

[Publications] 遠藤政夫: "Phosphoinositide hydrolysis and positive inotropic effect induced by endothelin in the rabbit ventricular muscle." Physiologist. 34. 110 (1991)

[Publications] 遠藤政夫: "Selective inhibition by stanrosporine and phorbol ester of the positive inotropic effect mediated by αー1 adrenergic receptors." Physiologist. 34. 110 (1991)

[Publications] 石幡明: "Influence of aging on the contractile response to endothelin of rat thoracic aorta." European Journal of Pharmacology. 200. 199-201 (1991)

[Publications] 遠藤政夫: "α,β受容体の生化学・薬理学" 綜合臨牀. 40. 2442-2449 (1991)

[Publications] 遠藤政夫: "心筋細胞内Ca動態と心筋収縮" 病態生理. 10. 430-436 (1991)

[Publications] 遠藤政夫: "心筋のαおよびβ受容体の意義" 臨床科学. 27. 334-339 (1991)