Angiotensin-(1-7) Induces Peripheral Antinociception through Mas Receptor Activation in an Opioid-Independent Pathway
Angiotensin-(1-7) Induces Peripheral Antinociception through Mas Receptor Activation in an Opioid-Independent Pathway
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DOI：
10.1159/000336340
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发表时间：
2012-01-01
期刊：
影响因子：
3.1
通讯作者：
Duarte, Igor D. G.
中科院分区：
文献类型：
--
作者：
Costa, Aline C. O.;Becker, Lenice K.;Duarte, Igor D. G.
G 蛋白偶联受体 Mas 最近被描述为血管紧张素-(1-7) [Ang-(1-7)] 受体。在本研究中，我们首次证明了 Ang-(17) 的抗伤害作用。此外，我们使用免疫荧光评估了 Mas 在背根神经节中的解剖定位。这是第一个证据表明该受体存在于敏感神经元中。使用大鼠爪压力测试证明了抗伤害作用。对于该测试，通过足底注射前列腺素 E-2 可以提高敏感性。将 Ang-(1-7) 局部注射到右后爪中会产生剂量依赖性的镇痛作用。因为较高剂量的 Ang-(1-7) 在注射到对侧爪子时没有产生作用，所以这种作用被认为是局部的。 Mas受体的特异性拮抗剂A-779以剂量依赖性方式抑制由暴露于4μg/爪Ang-(1-7)引起的外周镇痛作用。最高剂量完全逆转了 Ang-(1-7) 诱导的镇痛作用，表明 Mas 受体是该过程中的必需成分，而其他血管紧张素受体可能不参与其中。当单独注射时，拮抗剂不能引起痛觉过敏或镇痛。或者，纳洛酮无法抑制 Ang-(1-7) 诱导的镇痛作用，表明内源性阿片肽可能不参与这种反应。这些数据为 Ang-(1-7) 在不依赖阿片类药物的途径中通过 Mas 受体激活调节疼痛感知中的生理作用提供了第一个解剖学基础。总而言之，这些结果为开发一类新型镇痛药物提供了新的视角。版权所有 (C) 2012 S. Karger AG，巴塞尔
The G protein-coupled receptor Mas was recently described as an angiotensin-(1-7) [Ang-(1-7)] receptor. In the present study, we demonstrate an antinociceptive effect of Ang-(17) for the first time. Additionally, we evaluated the anatomical localization of Mas in the dorsal root ganglia using immunofluorescence. This is the first evidence indicating that this receptor is present in sensitive neurons. The antinociceptive effect was demonstrated using the rat paw pressure test. For this test, sensitivity is increased by intraplantar injection of prostaglandin E-2. Ang-(1-7) administered locally into the right hind paw elicited a dose-dependent antinociceptive effect. Because the higher dose of Ang-(1-7) did not produce an effect when injected into the contralateral paw, this effect was considered local. The specific antagonist for the Mas receptor, A-779, inhibited the peripheral antinociception induced by exposure to 4 mu g/paw Ang-(1-7) in a dose-dependent manner. The highest dose completely reversed the antinociceptive effect induced by Ang-(1-7), suggesting that the Mas receptor is an obligatory component in this process and that other angiotensin receptors may not be involved. When injected alone, the antagonist was unable to induce hyperalgesia or antinociception. Alternatively, naloxone was unable to inhibit the antinociceptive effect induced by Ang-(1-7), suggesting that endogenous opioid peptides may not be involved in this response. These data provide the first anatomical basis for the physiological role of Ang-(1-7) in the modulation of pain perception via Mas receptor activation in an opioid-independent pathway. Taken together, these results provide new perspectives for the development of a new class of analgesic drugs. Copyright (C) 2012 S. Karger AG, Basel