A NOVEL RADIOLIGAND [I-125] BQ-3020 SELECTIVE FOR ENDOTHELIN (ETB) RECEPTORS

被引：77

作者：

IHARA, M ^{[1
]}

SAEKI, T ^{[1
]}

FUKURODA, T ^{[1
]}

KIMURA, S ^{[1
]}

OZAKI, S ^{[1
]}

PATEL, AC ^{[1
]}

YANO, M ^{[1
]}

机构：

[1] AMERSHAM INT PLC,AMERSHAM HP7 9LL,BUCKS,ENGLAND

来源：

LIFE SCIENCES | 1992年 / 51卷 / 06期

关键词：

D O I：

10.1016/0024-3205(92)90418-O

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

A linear endothelin (ET) analog, N-acetyl-LeuMetAspLysGluAlaValTyrPheAlaHisLeuAspIleIleTrp (BQ-3020), is highly selective for ETB receptors. BQ-3020 displaces [I-125]ET-1 binding to ET(B) receptors (nonselective to ET isopeptides) in porcine cerebellar membranes (IC50: 0.2nM) at a concentration 4,700 times lower than that to ET(A) receptors (selective to ET-1) on aortic vascular smooth muscle cells (VSMC) (IC50: 940nM). BQ-3020 as well as ET-1 and ET-3 elicits vasoconstriction in the rabbit pulmonary artery. The ET(A) antagonist BQ-123 failed to inhibit this BQ-3020-induced vasocontraction. Furthermore, BQ-3020 elicits endothelium-dependent vasodilation. These data indicate that BQ-3020 has ET(B) agonistic activity. The radioligand [I-125]BQ-3020 binds to cerebellar membranes at single high affinity sites (Kd= 34.4pM), whereas it scarcely binds to VSMC. [I-125]BQ-3020 binding to the cerebellum was displaced by BQ-3020, ET-1 and ET-3 in a nonselective manner (IC50: 0.07-0.17nM). However, the binding of [I-125]BQ-3020 was insensitive to the ET(A) antagonist BQ-123 and other bioactive peptides. Both [I-125]ET-1 and [I-125]BQ-3020 show slow onset and offset binding kinetics to ET(B) receptors. These data indicate that the radioligand [I-125]BQ-3020 selectively labels ET(B) receptors and that the slow binding kinetics of ET-1 are dependent on the peptide sequence from LeU6 to Trp21, but not on the structure formed by its two disulfide bridges.

引用

页码：PL47 / PL52

页数：6

共 18 条

[1] CLONING AND EXPRESSION OF A CDNA-ENCODING AN ENDOTHELIN RECEPTOR [J].