Cloning, sequencing and functional expression of a guinea pig lung bradykinin B2 receptor

被引:28
作者
Farmer, SG
Powell, SJ
Wilkins, DE
Graham, A
机构
[1] Zeneca Pharmaceut, Biosci, Wilmington, DE 19850 USA
[2] Zeneca Pharmaceut, Macclesfield, Cheshire, England
关键词
bradykinin; bradykinin receptor; (guinea pig); bradykinin B-2 receptor; cloning; functional expression;
D O I
10.1016/S0014-2999(98)00024-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Kinin receptors are classified as B-1 and B-2 based upon agonist and antagonist potencies and cloning and expression studies. Using sequences from human and rat bradykinin B-2 receptors, polymerase chain reaction (PCR) was utilized to isolate cDNA from guinea pig lung. The receptor obtained is predicted to have 372 amino acids and shares > 80% sequence homology with human, rat, rabbit and mouse B-2 receptors. In competition binding experiments in Chinese hamster ovary (CHO-KI) cells in which the guinea pig cDNA was expressed, [H-3]bradykinin was displaced by kinin receptor ligands with an order of potency consistent with a B-2 subtype. In CHO cells expressing the guinea pig receptor, bradykinin caused a concentration Ca-45(2+) efflux. A B-1 receptor agonist, desArg(9)-bradykinin, also caused Ca-45(2+) efflux but with a potency several orders of magnitude lower than bradykinin. Curiously, several B-1 and B-2 receptor antagonists induced Ca-45(2+) efflux, indicating that this receptor may be coupled differently in CHO cells than in native tissues. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:291 / 298
页数:8
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