MacNeil T, Bierilo K K, Menke J G, Hess J F
Department of Molecular Pharmacology and Biochemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Biochim Biophys Acta. 1995 Nov 7;1264(2):223-8. doi: 10.1016/0167-4781(95)00152-7.
A rabbit B1 bradykinin receptor cDNA was isolated from a rabbit aorta smooth muscle cell library. The 1223 bp cDNA clone encodes a protein of 352 amino acids which is 78% identical to the human bradykinin B1(3) receptor protein. Heterologous expression of the rabbit B1 receptor cDNA in COS-7 cells imparts a high affinity specific binding for 3H-labeled [des-Arg10,Leu9]kallidin. Scatchard analysis indicates that the receptor binds the radiolabeled ligand with a Kd of 0.5 nM. The ability of kallidin (Lys-bradykinin) and bradykinin analogues to compete with binding of 3H-labeled [des-Arg10,Leu9]kallidin was determined and defined a rank order of potency: [des-Arg10,Leu9]kallidin = [des-Arg10]kallidin > [des- Arg9]bradykinin = kallidin >> bradykinin. This receptor exhibits the classical B1 pharmacological property of preferentially binding to kinin analogues which lack the C-terminal arginine. In addition, the affinities for [des-Arg10]kallidin and [des-Arg10,Leu9]kallidin are 100-fold higher than those for the corresponding bradykinin analogues [des-Arg9]bradykinin and [des-Arg9,Leu8]bradykinin which lack the N-terminal lysine. This pharmacological profile is characteristic of the B1 receptor subtype.
从兔主动脉平滑肌细胞文库中分离出兔B1缓激肽受体cDNA。该1223 bp的cDNA克隆编码一个由352个氨基酸组成的蛋白质，它与人类缓激肽B1(3)受体蛋白的同源性为78%。兔B1受体cDNA在COS-7细胞中的异源表达赋予了对3H标记的[去-精氨酸10，亮氨酸9]胰激肽的高亲和力特异性结合。Scatchard分析表明，该受体以0.5 nM的解离常数（Kd）结合放射性标记的配体。测定了胰激肽（赖氨酸-缓激肽）和缓激肽类似物与3H标记的[去-精氨酸10，亮氨酸9]胰激肽结合的竞争能力，并确定了效价顺序：[去-精氨酸10，亮氨酸9]胰激肽 = [去-精氨酸10]胰激肽 > [去-精氨酸9]缓激肽 = 胰激肽 >> 缓激肽。该受体表现出优先结合缺乏C末端精氨酸的激肽类似物的经典B1药理学特性。此外，[去-精氨酸10]胰激肽和[去-精氨酸10，亮氨酸9]胰激肽的亲和力比缺乏N末端赖氨酸的相应缓激肽类似物[去-精氨酸9]缓激肽和[去-精氨酸9，亮氨酸8]缓激肽高100倍。这种药理学特征是B1受体亚型的特点。
