THE G-PROTEINS OF THE G-ALPHA(I) AND G-ALPHA(Q) FAMILY COUPLED THE BRADYKININ RECEPTOR TO THE RELEASE OF ENDOTHELIUM-DERIVED RELAXING FACTOR

被引:108
|
作者
LIAO, JK
HOMCY, CJ
机构
[1] HARVARD UNIV,SCH MED,BOSTON,MA 02115
[2] COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032
[3] AMER CYANAMID CO,LEDERLE LABS,DIV MED RES,PEARL RIVER,NY 10965
来源
JOURNAL OF CLINICAL INVESTIGATION | 1993年 / 92卷 / 05期
关键词
PERTUSSIS TOXIN; CARBOXY-TERMINUS ANTISERA; HIGH AFFINITY AGONIST BINDING SITES; GTPASE ACTIVITY; WESTERN BUILDING;
D O I
10.1172/JCI116818
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
Bradykinin stimulates diverse functions in endothelial cells including the release of endothelium-derived relaxing factor (EDRF). Little is known, however, regarding the identity of the G protein(s) involved. Here we demonstrate that G proteins of the Galpha(i) and Galpha(q) family are coupled to the bradykinin receptor (BKR) in bovine aortic endothelial cells by using specific antisera directed against the COOH-terminal region of Galpha(i2) (P4), Galpha(i3) (EC), and Galpha(q) (QL). These antisera are specific since their effects are blocked by the decapeptides from which they were derived. The degree of receptor-G protein coupling was assessed by the formation of high affinity agonist binding sites (HABS) and GTP hydrolysis. In a concentration-dependent manner, the QL antisera reduced HABS and GTPase activity by 65 and 60%, respectively, and effectively abolished them in membranes from pertussis toxin-treated cells. The combination of P4 and EC antisera produced a loss of HABS (41%) and GTPase activity (40%) comparable to the effects of pertussis toxin. These findings indicate that Galpha(i) and Galpha(q) proteins mediate the cellular responses to bradykinin in bovine aortic endothelial cells and support the observation that bradykinin-stimulated EDRF release is relatively insensitive to pertussis toxin.
引用
收藏
页码:2168 / 2172
页数:5
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