Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, ed. 16, 90128, Palermo, Italy.
ATeN (Advanced Technologies Network) Center, University of Palermo, Viale delle Scienze, ed.18, 90128, Palermo, Italy.
J Physiol Biochem. 2022 Nov;78(4):753-762. doi: 10.1007/s13105-022-00892-7. Epub 2022 Apr 8.
The involvement of renin-angiotensin system in the modulation of gut motility and age-related changes in mRNA expression of angiotensin (Ang II) receptors (ATR) are well accepted. We aimed to characterize, in vitro, the contractile responses induced by Ang II, in jejunum from young (3-6 weeks old) and old rats (≥ 1 year old), to evaluate possible functional differences associated to changes in receptor expression. Mechanical responses to Ang II were examined in vitro as changes in isometric tension. ATR expression was assessed by qRT-PCR. Ang II induced a contractile effect, antagonized by losartan, AT1R antagonist, and increased by PD123319, AT2R antagonist, as well by neural blocker ω-conotoxin and by nitric oxide (NO) synthase inhibitor. No difference in the response was observed between young and old groups. AT1 receptor-mediated contractile response was decreased by U-73122, phospholipase C (PLC) inhibitor; or 2-aminoethoxy-diphenylborate (2-APB), inositol triphosphate (IP) receptor inhibitor; or nifedipine, L-type calcium channel blocker. Age-related changes in the expression of both AT1 receptor subtypes, AT1a and AT1b, and of AT2 receptors were detected. In conclusion, Ang II modulates the spontaneous contractility of rat jejunum via postjunctional AT1 receptors, involving Ca mobilization from intracellular stores, via PLC/IP pathway, and Ca influx from extracellular space, via L-type channels. Prejunctional AT2 receptors would counteract AT1 receptor effects, via NO synthesis. The observed age-related differences in the expression of all AT receptor subtypes are not reflected in the muscular contractile response to Ang II.
肾素-血管紧张素系统（renin-angiotensin system）在调节肠道动力以及与年龄相关的血管紧张素（Ang II）受体（ATR）mRNA 表达变化中起着重要作用，这一点已得到广泛认可。我们的目的是在体外研究 Ang II 诱导的收缩反应，使用来自年轻（3-6 周龄）和老年（≥1 岁）大鼠的空肠组织，评估与受体表达变化相关的可能的功能差异。通过等长张力变化来检测 Ang II 引起的机械反应。通过 qRT-PCR 评估 ATR 的表达。Ang II 诱导收缩效应，该效应被 losartan（AT1R 拮抗剂）拮抗，被 PD123319（AT2R 拮抗剂）增强，还被神经阻断剂 ω-conotoxin 和一氧化氮（NO）合酶抑制剂增强。在年轻组和老年组之间未观察到反应的差异。AT1 受体介导的收缩反应被 U-73122（PLC 抑制剂）、2-氨基乙氧基二苯硼酸盐（2-APB，三磷酸肌醇（IP）受体抑制剂）或硝苯地平（L 型钙通道阻滞剂）减弱。检测到与年龄相关的 AT1 受体亚型（AT1a 和 AT1b）和 AT2 受体的表达变化。总之，Ang II 通过位于突触后的 AT1 受体调节大鼠空肠的自发性收缩性，该受体通过 PLC/IP 途径从细胞内库中动员 Ca2+，并通过 L 型通道从细胞外空间中流入 Ca2+。位于突触前的 AT2 受体通过 NO 合成来拮抗 AT1 受体的作用。观察到的与年龄相关的所有 AT 受体亚型的表达差异并未反映在 Ang II 对肌肉收缩反应上。
