Role of endothelin in the physiological closure of Ductus Artenosus

内皮素在动脉导管生理闭合中的作用

• 批准号: 14570076
• 负责人: TANIGUCHI Takanobu
• 金额: $ 2.3万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570076/
• 关键词: Ductuc Artenosus; endothelin; indomethacin

1)Ductus arteriosus(DA) undergoes rapid closure after birth as pulmonary circulation is established The mechanism of the closure is controversial regarding an involvement of endothelin(ET).2)The effect of ATZ1993(ATZ), a non-peptide antagonist for the ET_A and ET_B receptors, on postnatal closure and O_2-induced contraction of the rat DA was investigated both in vivo and in vitro. Rat pups were delivered by Caesarean section and were given ATZ intraperitoneally. The minimum external DA diameter and the extent of DA constriction in vivo were evaluated at 25 h after birth. ATZ caused a dose-dependent inhibition of DA closure in vivo. When rat pups were given ATZ at 2.5 h after birth, re-opening of the DA was observed.3)In vitro, ATZ also caused a marked inhibition of O_2-induced and ET1-induced DA contractions as did BQ123, a ET_A-specific antagonist. In contrast, sarafotoxin S6c, an ET_B-specific agonist, did not cause DA contraction and BQ 788, an ET_B-specific antagonist, did not affect O_2-induced DA contraction.4)ET and its cognate receptor ET_A can play a physiological role in the postnatal closure of the rat DA in vivo.

1)2）用ET_A和ET_B受体的非肽类拮抗剂ATZ 1993（ATZ），在体和离体条件下，研究了ATZ 1993对新生大鼠肺动脉（DA）闭合和O_2引起的收缩的影响。通过剖腹产术分娩大鼠幼崽，并腹腔内给予ATZ。在生后25 h测量DA最小外径和DA缩窄程度。ATZ在体内可剂量依赖性地抑制DA受体的关闭。在体外，ATZ和ET_A特异性拮抗剂BQ_（123）对O_2和ET_（1）引起的DA收缩也有明显的抑制作用。ET_B特异性激动剂sarafotoxin S6c不引起DA收缩，而ET_B特异性拮抗剂BQ 788不影响O_2引起的DA收缩。4）ET及其同源受体ET_A在大鼠DA的生后关闭过程中起生理作用。

项目成果

Takahashi M, Taniguchi T, Tanaka T, Kanamaru H, Murarnatsu: "Pharmacological characterization of TA-O201, an endothelin receptor antagonist, with recombinant and human prostate endothelin receptors"Eur J Pharmacol. 467(1-3). 185-189 (2003)

Takahashi M、Taniguchi T、Tanaka T、Kanamaru H、Murarnatsu：“TA-O201（一种内皮素受体拮抗剂，具有重组和人前列腺内皮素受体）的药理学特征”Eur J Pharmacol。

Yamada T, Taniguchi T, Shiokoshi T, Narumiya S, Ushikubi F.: "Thromboxane A2 regulates vascular tone via its inhibitory effect on the expression of inducible nitric oxide synthase"Circulation. 108(19). 2381-2386 (2003)

Yamada T、Taniguchi T、Shiokoshi T、Narumiya S、Ushikubi F.：“血栓烷 A2 通过其对诱导型一氧化氮合酶表达的抑制作用来调节血管张力”循环。

Takahashi M, Taniguchi_T, Tanaka T, Kanamaru H, Muramatsu I.: "Pharmacological characterization of TA-0201, an endothelia receptor antagonist, with recombinant and human prostate endothelin receptors"Eur J Pharmacol. 467(1-3). 185-189 (2003)

Takahashi M、Taniguchi_T、Tanaka T、Kanamaru H、Muramatsu I.：“TA-0201（一种内皮受体拮抗剂，具有重组和人前列腺内皮素受体）的药理学特征”Eur J Pharmacol。

Ishida A, Shigeri Y, Taniguchi T, Kameshita I.: "Protein phosphatases that regulate multifunctional Ca2+/calmodulin-dependent protein kinases : from biochemistry to pharmacology"Pharmacol Ther. 100(3). 291-305 (2003)

Ishida A、Shigeri Y、Taniguchi T、Kameshita I.：“调节多功能 Ca2/钙调蛋白依赖性蛋白激酶的蛋白磷酸酶：从生物化学到药理学”Pharmacol Ther。

Taniguchi T, Muramatsu I.: "Pharmacological knockout of endothelin ET(A) receptors"Life Sci. 74(2-3). 405-409 (2003)

Taniguchi T、Muramatsu I.：“内皮素 ET(A) 受体的药理学敲除”生命科学。