Sato Akira, Yokoyama Izumi, Ebina Keiichi
Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima 970-8551, Japan.
Faculty of Pharmacy, Iwaki Meisei University, 5-5-1, Chuodai-Iino, Iwaki, Fukushima 970-8551, Japan.
Peptides. 2015 Nov;73:60-6. doi: 10.1016/j.peptides.2015.09.002. Epub 2015 Sep 5.
Angiotensin (Ang)--a peptide that is part of the renin-angiotensin system-induces vasoconstriction and a subsequent increase in blood pressure; Ang peptides, especially AngII, can also act as potent pro-inflammatory mediators. Platelet-activating factor (PAF) is a potent phospholipid mediator that is implicated in many inflammatory diseases. In this study, we investigated the effects of Ang peptides (AngII, AngIII, and AngIV) on PAF-induced inflammatory activity. In experiments using a rat hind-paw oedema model, AngII markedly and dose-dependently attenuated the paw oedema induced by PAF. The inhibitory effects of AngIII and AngIV on PAF-induced paw oedema were lower than that of AngII. Two Ang receptors, the AT1 and AT2 receptors, did not affect the AngII-mediated attenuation of PAF-induced paw oedema. Moreover, intrinsic tyrosine fluorescence studies demonstrated that AngII, AngIII, and AngIV interact with PAF, and that their affinities were closely correlated with their inhibitory effects on PAF-induced rat paw oedema. Also, AngII interacted with metabolite/precursor of PAF (lyso-PAF), and an oxidized phospholipid, 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), which bears a marked structural resemblance to PAF. Furthermore, POVPC dose-dependently inhibited AngII-mediated attenuation of PAF-induced paw oedema. These results suggest that Ang peptides can attenuate PAF-induced inflammatory activity through binding to PAF and lyso-PAF in rats. Therefore, Ang peptides may be closely involved in the regulation of many inflammatory diseases caused by PAF.
血管紧张素（Ang）——肾素-血管紧张素系统的一种肽——可诱导血管收缩并随后使血压升高；Ang肽，尤其是AngII，还可作为强效促炎介质。血小板活化因子（PAF）是一种强效磷脂介质，与多种炎症性疾病有关。在本研究中，我们研究了Ang肽（AngII、AngIII和AngIV）对PAF诱导的炎症活性的影响。在使用大鼠后爪水肿模型的实验中，AngII显著且剂量依赖性地减轻了PAF诱导的爪水肿。AngIII和AngIV对PAF诱导的爪水肿的抑制作用低于AngII。两种Ang受体，即AT1和AT2受体，不影响AngII介导的对PAF诱导的爪水肿的减轻作用。此外，内在酪氨酸荧光研究表明，AngII、AngIII和AngIV与PAF相互作用，且它们的亲和力与其对PAF诱导的大鼠爪水肿的抑制作用密切相关。此外，AngII与PAF的代谢物/前体（溶血PAF）以及一种氧化磷脂1-棕榈酰-2-（5'-氧代戊酰基）-sn-甘油-3-磷酸胆碱（POVPC）相互作用，POVPC与PAF具有明显的结构相似性。此外，POVPC剂量依赖性地抑制AngII介导的对PAF诱导的爪水肿的减轻作用。这些结果表明，Ang肽可通过与大鼠体内的PAF和溶血PAF结合来减轻PAF诱导 的炎症活性。因此，Ang肽可能密切参与由PAF引起的多种炎症性疾病的调节。
