Endothelin receptor subtype and physiology of vascular smooth muscle and endothelium

内皮素受体亚型与血管平滑肌和内皮的生理学

• 批准号: 04454115
• 负责人: OZAKI Hiroshi
• 金额: $ 4.16万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454115/
• 关键词: endothelin; receptor; smooth muscle; endothelium; pharmacology; calcium

It is generally accepted that endothelin A receptors (ET_A) are more abundant in smooth muscle and the activation of this receptor subtype contributes to smooth muscle contraction. On the other hand ET_Bs are distributed in endothelial cells and these receptors contribute to the production of NO or prostacyclin. We first demonstrated in this study that ET_B is subdivided into ET_<B1> and ET_<B2> by using selective endothelin blockers. Further, it was found that ET_As are also subdivided into ET_<A1> and ET_<A2>. We also found that endothelins act selectively on the EA_A receptor to increase[Ca^<2+>]_i in the endothelium of rabbit aortic valve. The above findings may contribute to the understanding of physiological and pathophysiological role of endothelin.

人们普遍认为，内皮素A受体(ET_A)在血管内皮细胞中含量较高，该受体亚型的激活有助于血管收缩。另一方面，ET_B分布于内皮细胞，这些受体参与NO或前列环素的产生。在本研究中，我们首次通过使用选择性内皮素阻滞剂将ET_B细分为ET_1、B1和Gt；此外，还发现ET_AS还细分为ET_&lt；A1&gt；和ET_&lt；A2&gt；我们还发现，内皮素选择性地作用于EA_A受体，使兔主动脉瓣内皮细胞[Ca~(2+)]_i升高。上述结果可能有助于了解内皮素的生理和病理生理作用。

项目成果

SANAGI,M.: "Mechanisms of relaxing action of the antiasthmatic drug,azelastine,in isolated porcine tracheal smooth muscle." Eur.J.Pharmacol. 222. 247-255 (1992)

SANAGI,M.：“抗哮喘药物氮卓斯汀对离体猪气管平滑肌的松弛作用机制。”

KARAKI,H: "Induction of endothelium-dependent relaxation in the rat aorta by IRL1620,a novel and selective agonist at the endothelin ETB receptor." Br.J.Pharmacol. 109. 486-490 (1993)

KARAKI,H：“IRL1620 是一种新型选择性内皮素 ETB 受体激动剂，可诱导大鼠主动脉内皮依赖性舒张。”

KARAKI,H.: "ET_B receptor antagonist,IRL1038,Selectively inhibits the endothelin-induced endothelium-dependent vascular relaxation." Eur.J.Pharmacol.231. 371-374 (1993)

KARAKI,H.：“ET_B 受体拮抗剂，IRL1038，选择性抑制内皮素诱导的内皮依赖性血管舒张。”

H.Ozaki: "Mechanism of vasodilator" Blood vescle. 16. 101-105 (1993)

H.Ozaki：“血管扩张剂的机制”血管。

HORI,M.,SATO,K.,MIYAMOTO,S.,OZAKI,H.& KARAKI,H.: "Different pathways of calcium sensitization activated by receptor agonists and phorbol esters in vascular smooth muscle." Br.J.Pharmacol. 110. 1527-1531 (1993)

堀M.、佐藤K.、宫本S.、尾崎H.