College of Pharmacy, Nova Southeastern University, Ft. Lauderdale, FL, 33328, USA.
Behavioral Neuroscience Program, Department of Psychology, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
Endocrine. 2019 Nov;66(2):349-359. doi: 10.1007/s12020-019-01930-z. Epub 2019 Apr 24.
To study the ability of a novel bovine serum albumin-angiotensin II (BSA-Ang II) conjugate to effect responses of the AT angiotensin II receptor subtype mediated by the G-protein-coupled and the beta-arrestin pathways.
Angiotensin II (Ang II) was conjugated with bovine serum albumin and compared with Ang II for competition binding to AT receptors, to stimulate aldosterone release from adrenocortical cells, to promote beta-arrestin binding to AT receptors, to promote calcium mobilization, and stimulate drinking of water and saline by rats.
The BSA-Ang II conjugate was less potent competing for ATR binding, but was equally efficacious at stimulating aldosterone release from H295R adrenocortical cells. Both BSA-Ang II and Ang II stimulated calcium mobilization and beta-arrestin binding to AT receptors. BSA-Ang II and Ang II stimulated water appetite equivalently but BSA-Ang II stimulated saline appetite more than Ang II. Both BSA-Ang II and Ang II were considerably more potent at causing calcium mobilization than β-arrestin binding.
Addition of a high molecular weight molecule to Ang II reduced its AT receptor binding affinity, but did not significantly alter stimulation of aldosterone release or water consumption. The BSA-Ang II conjugate caused a greater saline appetite than Ang II suggesting that it may be a more efficacious agonist of this beta-arrestin-mediated response than Ang II. The higher potency calcium signaling response suggests that the G-protein-coupled responses predominate at physiological concentrations of Ang II, while the beta-arrestin response requires pathophysiological or pharmacological concentrations of Ang II to occur.
研究一种新型牛血清白蛋白-血管紧张素 II（BSA-Ang II）缀合物对 G 蛋白偶联和β-arrestin 通路介导的 AT 血管紧张素 II 受体亚型反应的作用能力。
将血管紧张素 II（Ang II）与牛血清白蛋白缀合，并与 Ang II 竞争结合 AT 受体、刺激肾上腺皮质细胞释放醛固酮、促进β-arrestin 与 AT 受体结合、促进钙动员以及刺激大鼠饮水和盐水摄入进行比较。
BSA-Ang II 缀合物对 ATR 结合的竞争能力较弱，但刺激 H295R 肾上腺皮质细胞释放醛固酮的效力相等。BSA-Ang II 和 Ang II 均刺激钙动员和β-arrestin 与 AT 受体结合。BSA-Ang II 和 Ang II 引起的水食欲相等，但 BSA-Ang II 引起的盐水食欲比 Ang II 更强。BSA-Ang II 和 Ang II 引起钙动员的效力均明显强于β-arrestin 结合。
向 Ang II 中添加高分子量分子降低了其 AT 受体结合亲和力，但对刺激醛固酮释放或水摄入没有显著影响。BSA-Ang II 缀合物引起的盐水食欲大于 Ang II，这表明它可能是比 Ang II 更有效的该β-arrestin 介导反应的激动剂。钙信号转导的高反应性提示，在 Ang II 的生理浓度下，G 蛋白偶联反应占主导地位，而β-arrestin 反应需要 Ang II 的病理生理或药理学浓度才能发生。
