Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Human Microbiome Research Programme, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
J Int Med Res. 2022 Jun;50(6):3000605221105163. doi: 10.1177/03000605221105163.
To investigate the regulation of local aldosterone synthesis by physiological stimulants in the murine gut.
Male mice were fed for 14 days with normal, high (1.6%) or low (0.01%) sodium diets. Tissue liver receptor homolog-1 and aldosterone in the colon and caecum were detected using an enzyme-linked immunosorbent assay (ELISA). Released corticosterone and aldosterone in tissue incubation experiments after stimulation with angiotensin II (Ang II) and dibutyryl-cAMP (DBA; the second messenger of adrenocorticotropic hormone) were assayed using an ELISA. Tissue aldosterone synthase (CYP11B2) protein levels were measured using an ELISA and Western blots.
In incubated colon tissues, aldosterone synthase levels were increased by a low-sodium diet; and by Ang II and DBA in the normal diet group. Release of aldosterone into the incubation buffer was increased from the colon by a low-sodium diet and decreased by a high-sodium diet in parallel with changes in aldosterone synthase levels. In mice fed a normal diet, colon incubation with both Ang II and DBA increased the release of aldosterone as well as its precursor corticosterone.
Local aldosterone synthesis in the large intestine is stimulated by a low-sodium diet, dibutyryl-cAMP and Ang II similar to the adrenal glands.
研究生理刺激物对肠道中局部醛固酮合成的调节作用。
雄性小鼠连续 14 天分别用正常、高(1.6%)或低(0.01%)钠饮食喂养。采用酶联免疫吸附试验(ELISA)检测结肠和盲肠组织肝受体同源物-1 和醛固酮。用 ELISA 检测组织孵育实验中血管紧张素 II(Ang II)和二丁酰环磷酸腺苷(DBA;促肾上腺皮质激素的第二信使)刺激后释放的皮质酮和醛固酮。采用 ELISA 和 Western blot 法检测组织醛固酮合酶(CYP11B2)蛋白水平。
在孵育的结肠组织中,低钠饮食可增加醛固酮合酶水平;在正常饮食组中,Ang II 和 DBA 也可增加醛固酮合酶水平。低钠饮食增加了孵育缓冲液中醛固酮的释放,而高钠饮食则与醛固酮合酶水平的变化平行降低了其释放。在正常饮食喂养的小鼠中,Ang II 和 DBA 孵育结肠均可增加醛固酮及其前体皮质酮的释放。
与肾上腺相似,低钠饮食、二丁酰环磷酸腺苷和 Ang II 刺激大肠局部醛固酮合成。