Vinson G P, Ho M M, Puddefoot J R, Teja R, Barker S
Department of Biochemistry, Faculty of Basic Medical Sciences, Queen Mary and Westfield College, London, U.K.
J Endocrinol. 1994 May;141(2):R5-9. doi: 10.1677/joe.0.141r005.
Little is known about the cellular localisation of the angiotensin II (AII) type 1 receptor (AT1) in the rat adrenal glomerulosa cell, but some studies have suggested that receptor internalisation and recycling may occur. Using a specific monoclonal antibody (6313/G2) to the first extracellular domain, we show here that most of the receptor is internalised in the unstimulated cell. When viable glomerulosa cells are incubated with 6313/G2, the receptor is transiently concentrated on the cell surface, and aldosterone output is stimulated. This stimulated output is enhanced by neither threshold nor maximal stimulatory concentrations of AII amide, although the antibody does not inhibit AII binding to the receptor. Conversely, the stimulatory actions of the antibody and those of ACTH are additive. The data suggest that recycling to the plasma membrane is constitutive, or regulated by unknown factors. Retention of the AT1 receptor in the membrane is alone enough to allow sufficient G protein interaction to generate maximal stimulatory events.
关于血管紧张素II(AII)1型受体(AT1)在大鼠肾上腺球状带细胞中的细胞定位,目前所知甚少,但一些研究表明可能会发生受体内化和再循环。使用针对第一个细胞外结构域的特异性单克隆抗体(6313/G2),我们在此表明,大多数受体在未受刺激的细胞中发生内化。当活的球状带细胞与6313/G2一起孵育时,受体会短暂地集中在细胞表面,并刺激醛固酮的分泌。尽管该抗体不抑制AII与受体的结合,但AII酰胺的阈值浓度或最大刺激浓度均不会增强这种刺激的分泌。相反,抗体的刺激作用与促肾上腺皮质激素(ACTH)的刺激作用具有相加性。数据表明,向质膜的再循环是组成性的,或受未知因素调节。AT1受体保留在膜上本身就足以允许足够的G蛋白相互作用以产生最大刺激事件。