Douglas J, Aguilera G, Kondo T, Catt K
Endocrinology. 1978 Mar;102(3):685-96. doi: 10.1210/endo-102-3-685.
Specific receptors for angiotensin II (A II) were demonstrated in membrane fractions and collagenase-dispersed cells from the zona glomerulosa of the rat adrenal gland. The equilibrium association constant (Ka) of the A II binding sites was similar in particulate fractions (2.0 +/- 0.4 (SE) X 10(9) M-1) and intact glomerulosa cells (1.8 +/- 0.3 X 10(9) M-1). Specific binding of [125I]iodo-A II was enhanced by increasing sodium concentration, and in the presence of dithiothreitol, EDTA, and EGTA. Plasma membrane fractions prepared by density gradient centrifugation showed increased binding of [125I]iodo-A II, and were correspondingly enriched in adenylate cyclase and sodium-potassium-dependent ATPase. Steroid production by collagenase-dispersed adrenal glomerulosa cells was highly responsive to A II and ACTH. Significant increases in aldosterone and corticosterone production were elicited by A II concentrations as low as 3 X 10(-11) M, equivalent to normal blood levels of A II in rats (5 X 10(-11) M). The maximum increase in aldosterone production, of 6--7 times the basal value, was obtained at 10(-9) M A II. Dispersed capsular cells were also highly sensitive to ACTH, responding to concentrations down to 3 X 10(-12) M with increased aldosterone production, reaching a maximum aldosterone response of 20-fold above the basal value. The magnitudes of the aldosterone and corticosterone responses to A II in capsular and fasciculata-reticularis cells were commensurate with the distribution of A II receptors, which were 11-fold more concentrated in capsular cells. The ability of A II to evoke aldosterone production at physiological concentrations, and the correspondence between A II binding and steroidogenesis in capsular cells, demonstrate the functional importance of A II receptor sites in the zona glomerulosa of the rat adrenal cortex.
在大鼠肾上腺球状带的膜组分和经胶原酶分散的细胞中证实了血管紧张素II(A II)的特异性受体。A II结合位点的平衡缔合常数(Ka)在微粒体组分(2.0±0.4(SE)×10⁹ M⁻¹)和完整的球状带细胞(1.8±0.3×10⁹ M⁻¹)中相似。[¹²⁵I]碘代 - A II的特异性结合在增加钠浓度以及存在二硫苏糖醇、EDTA和EGTA的情况下增强。通过密度梯度离心制备的质膜组分显示[¹²⁵I]碘代 - A II的结合增加,并且相应地富含腺苷酸环化酶和钠钾依赖性ATP酶。经胶原酶分散的肾上腺球状带细胞的类固醇生成对A II和促肾上腺皮质激素(ACTH)高度敏感。低至3×10⁻¹¹ M的A II浓度即可引起醛固酮和皮质酮生成的显著增加,这相当于大鼠血液中A II的正常水平(5×10⁻¹¹ M)。在10⁻⁹ M A II时,醛固酮生成的最大增加量为基础值的6 - 7倍。分散的被膜细胞对ACTH也高度敏感,对低至3×10⁻¹² M的浓度有反应,醛固酮生成增加,醛固酮的最大反应比基础值高20倍。被膜细胞和束状带 - 网状带细胞中醛固酮和皮质酮对A II的反应幅度与A II受体的分布相称,A II受体在被膜细胞中的浓度高11倍。A II在生理浓度下诱发醛固酮生成的能力以及A II结合与被膜细胞中类固醇生成之间的对应关系,证明了A II受体位点在大鼠肾上腺皮质球状带中的功能重要性。