The Northeast Biotechnology Network (RENORBIO), Federal University of Piauí, Teresina, PI 64049-550, Brazil; Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (Lafidg), Federal University of Parnaíba Delta (UFDPar), Av. São Sebastião, n° 2819, CEP 64202-02 Parnaíba, PI, Brazil.
Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE 60430-275, Brazil.
Biochem Pharmacol. 2021 Apr;186:114500. doi: 10.1016/j.bcp.2021.114500. Epub 2021 Mar 6.
The angiotensin (Ang) II converting enzyme (ACE II) pathway has recently been shown to be associated with several beneficial effects on the body, especially on the cardiac system and gastrointestinal tract. ACE II is responsible for converting Ang II into the active peptide Ang-(1-7), which in turn binds to a metabotropic receptor, the Mas receptor (MasR). Recent studies have demonstrated that Diminazene Aceturate (DIZE), a trypanosomicide used in animals, activates the ACE II pathway. In this study, we aimed to evaluate the antidiarrheal effects promoted by the administration of DIZE to activate the ACE II/Ang-(1-7)/MasR axis in induced diarrhea mice models. The results show that activation of the ACE II pathway exerts antidiarrheal effects that reduce total diarrheal stools and enteropooling. In addition, it increases Na/K-ATPase activity and reduces gastrointestinal transit and thus inhibits contractions of intestinal smooth muscle; decreases transepithelial electrical resistance, epithelial permeability, PGE2-induced diarrhea, and proinflammatory cytokines; and increases anti-inflammatory cytokines. Enzyme-linked immunosorbent assay (ELISA) demonstrated that DIZE, when activating the ACE II/Ang-(1-7)/MasR axis, can still interact with GM1 receptors, which reduces cholera toxin-induced diarrhea. Therefore, activation of the ACE II/Ang-(1-7)/MasR axis can be an important pharmacological target for the treatment of diarrheal diseases.
血管紧张素（Ang）II 转化酶（ACE II）途径最近已被证明与身体的几种有益作用有关，特别是对心脏系统和胃肠道。ACE II 负责将 Ang II 转化为活性肽 Ang-(1-7)，后者反过来与代谢型受体 Mas 受体（MasR）结合。最近的研究表明，用于动物的驱虫药苯唑硝唑（DIZE）激活 ACE II 途径。在这项研究中，我们旨在评估 DIZE 给药激活 ACE II/Ang-(1-7)/MasR 轴对诱导性腹泻小鼠模型的抗腹泻作用。结果表明，激活 ACE II 途径具有抗腹泻作用，可减少总腹泻粪便和肠液积聚。此外，它增加了 Na/K-ATPase 活性，减少了胃肠道转运，从而抑制了肠平滑肌的收缩；降低了跨上皮电阻、上皮通透性、PGE2 诱导的腹泻和促炎细胞因子；并增加了抗炎细胞因子。酶联免疫吸附试验（ELISA）表明，DIZE 在激活 ACE II/Ang-(1-7)/MasR 轴时，仍能与 GM1 受体相互作用，从而减少霍乱毒素诱导的腹泻。因此，激活 ACE II/Ang-(1-7)/MasR 轴可能是治疗腹泻病的重要药理学靶点。
