Liao J K, Homcy C J
Cardiovascular Division, Brigham & Women's Hospital, Boston, Massachusetts 02115.
J Clin Invest. 1993 Nov;92(5):2168-72. doi: 10.1172/JCI116818.
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 G alpha i and G alpha 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 G alpha i2 (P4), G alpha i3 (EC), and G alpha 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 G alpha i and G alpha 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.
缓激肽可刺激内皮细胞发挥多种功能,包括释放内皮源性舒张因子(EDRF)。然而,关于所涉及的G蛋白的身份却知之甚少。在此,我们通过使用针对Gαi2(P4)、Gαi3(EC)和Gαq(QL)的COOH末端区域的特异性抗血清,证明了Gαi和Gαq家族的G蛋白与牛主动脉内皮细胞中的缓激肽受体(BKR)偶联。这些抗血清具有特异性,因为它们的作用可被其来源的十肽所阻断。通过高亲和力激动剂结合位点(HABS)的形成和GTP水解来评估受体 - G蛋白偶联的程度。QL抗血清以浓度依赖的方式分别使HABS和GTP酶活性降低65%和60%,并在百日咳毒素处理的细胞的膜中有效地消除了它们。P4和EC抗血清的组合导致HABS(41%)和GTP酶活性(40%)的丧失,与百日咳毒素的作用相当。这些发现表明,Gαi和Gαq蛋白介导了牛主动脉内皮细胞对缓激肽的细胞反应,并支持缓激肽刺激的EDRF释放对百日咳毒素相对不敏感的观察结果。