Nakamichi K, Ihara M, Kobayashi M, Saeki T, Ishikawa K, Yano M
Central Research Labs., Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Biochem Biophys Res Commun. 1992 Jan 15;182(1):144-50. doi: 10.1016/s0006-291x(05)80123-8.
We have demonstrated the different distribution of two distinct endothelin (ET) receptor subtypes in porcine pulmonary tissues using a radioligand binding assay. The clear differentiation of the subtypes was made possible by the discovery of two compounds, BQ-123 and [Ala1,3,11,15]ET-1 (4AlaET-1), that are highly selective for ETA and ETB receptors, respectively. In the bronchus and lung parenchyma, BQ-123 inhibited 65% and 30% of [125I]ET-1 binding on the sensitive sites, while 4AlaET-1 displaced 25% and 60%, respectively. The combination of the two compounds completely inhibited ET-1 binding in both tissues. An autoradiographic study of [125I]ET-1 binding using BQ-123 and 4AlaET-1 also supported the different localization of two ET receptor subtypes in pulmonary tissues. In particular, the blood vessels and bronchi are rich in ETA, but the lung parenchyma is rich in ETB.
我们利用放射性配体结合试验证明了两种不同的内皮素（ET）受体亚型在猪肺组织中的不同分布。两种化合物BQ-123和[Ala1,3,11,15]ET-1（4AlaET-1）的发现使得亚型的清晰区分成为可能，它们分别对ETA和ETB受体具有高度选择性。在支气管和肺实质中，BQ-123分别抑制了敏感位点上65%和30%的[125I]ET-1结合，而4AlaET-1分别取代了25%和60%。这两种化合物的组合完全抑制了两种组织中的ET-1结合。使用BQ-123和4AlaET-1对[125I]ET-1结合进行的放射自显影研究也支持了两种ET受体亚型在肺组织中的不同定位。特别是，血管和支气管富含ETA，但肺实质富含ETB。
