Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.
Peptides. 2013 Jan;39:21-8. doi: 10.1016/j.peptides.2012.10.012. Epub 2012 Nov 8.
In our previous study, we showed that intrathecal (i.t.) administration of angiotensin IV (Ang IV), an insulin-regulated aminopeptidase (IRAP) inhibitor, attenuated inflammatory hyperalgesia in rats. Using the plantar test in rats with carrageenan-induced paw inflammation, we investigated the possible mechanism(s) of this effect. Because i.t. oxytocin was reported to produce a dose-dependent anti-hyperalgesia in rats with inflammation, we speculate that there is a possible correlation between oxytocin-induced and Ang IV-induced anti-hyperalgesia. Using i.t. co-administered atosiban (oxytocin receptor antagonist), the anti-hyperalgesia by Ang IV was completely abolished. This indicated that oxytocin could be the major IRAP substrate responsible for the anti-hyperalgesia by Ang IV. When Ang IV was co-administered with a low dose of oxytocin, there was a significant enhancing effect of Ang IV on oxytocin-induced anti-hyperalgesia. In recent reports, electrical stimulation on the paraventricular hypothalamic nucleus (PVN) was proved to increase oxytocin release at the spinal cord. Our results also showed that Ang IV could prolong the anti-hyperalgesia induced by PVN stimulation. This suggests a possible protective effect of Ang IV on endogenous oxytocin degradation/dysfunctioning. Moreover, we examined the local effect of intraplantarly injected Ang IV in the same model. Our results showed no effect of local Ang IV on hyperalgesia and paw edema, indicating that Ang IV may not regulate the peripheral inflammatory process. Overall, our study suggests that Ang IV may act through the inhibition of the activity of IRAP to reduce the degradation of oxytocin at the spinal cord, thereby leading to anti-hyperalgesia in rats with inflammation.
在我们之前的研究中，我们表明鞘内（i.t.）给予血管紧张素 IV（Ang IV），一种胰岛素调节的氨基肽酶（IRAP）抑制剂，可减轻大鼠的炎症性痛觉过敏。使用角叉菜胶诱导的爪炎症大鼠的足底测试，我们研究了这种作用的可能机制。由于报道 i.t.催产素在炎症大鼠中产生剂量依赖性的抗痛觉过敏作用，我们推测催产素诱导的和 Ang IV 诱导的抗痛觉过敏之间可能存在相关性。使用 i.t.共同给予阿托西班（催产素受体拮抗剂），Ang IV 的抗痛觉过敏作用完全被消除。这表明催产素可能是负责 Ang IV 抗痛觉过敏的主要 IRAP 底物。当 Ang IV 与低剂量催产素共同给予时，Ang IV 对催产素诱导的抗痛觉过敏有显著增强作用。在最近的报道中，证明电刺激室旁下丘脑核（PVN）可增加脊髓中的催产素释放。我们的结果还表明，Ang IV 可以延长 PVN 刺激引起的抗痛觉过敏。这表明 Ang IV 对内源性催产素降解/功能障碍可能具有保护作用。此外，我们在相同模型中检查了局部注射 Ang IV 的局部效应。我们的结果显示局部 Ang IV 对痛觉过敏和爪水肿没有影响，表明 Ang IV 可能不会调节外周炎症过程。总体而言，我们的研究表明 Ang IV 可能通过抑制 IRAP 的活性来减少脊髓中催产素的降解，从而导致炎症大鼠的抗痛觉过敏。
