Activation of peripheral galanin receptors:: Differential effects on nociception
Activation of peripheral galanin receptors:: Differential effects on nociception
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DOI：
10.1016/j.pbb.2006.08.008
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发表时间：
2006-09-01
影响因子：
3.6
通讯作者：
Carlton, Susan M.
中科院分区：
文献类型：
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作者：
Jimenez-Andrade, Juan Miguel;Lundstrom, Linda;Carlton, Susan M.
大量报告表明外周甘丙肽 (GAL) 在疼痛传递中发挥着重要作用；然而，由于缺乏选择性甘丙肽受体激动剂和拮抗剂，GAL受体（GalR1-3）在疼痛传递中的作用仍不清楚。在本研究中，在外周测试了优先结合 GalR1 的新型激动剂 M617、GalR2 激动剂 (AR-M1896) 和 GalR2 拮抗剂 (M871)，以阐明外周 GalR1 和 GalR2 在伤害感受中的作用。同侧（而非对侧）后爪注射 M617 可使辣椒素 (CAP) 诱导的退缩减少约 50%，表明 GalR1 激活可产生抗伤害作用。这种抗伤害作用可以通过足底注射非选择性 GalR 拮抗剂 M35 来阻断。相比之下，足底注射 GalR2 激动剂 AR-M1896 增强了同侧而非对侧的 CAP 诱导的伤害感受（1.7 倍）。 GalR2 拮抗剂 M871 以剂量依赖性方式阻断 AR-M1896 的促伤害作用。该拮抗剂对单独 CAP 诱导的伤害性行为没有影响。数据表明，外周 GalR1 的激活会产生抗伤害感受，但外周 GalR2 的激活会产生促伤害感受。因此，使用这些药理学工具可能有助于阐明 GalR 亚型在伤害感受处理中的作用，确定治疗外周疼痛的潜在药物靶点。 (c) 2006 Elsevier Inc. 保留所有权利。
Numerous reports suggest a significant role of peripheral galanin (GAL) in pain transmission; however, due to the lack of selective galanin receptor agonists and antagonists, the role of GAL receptors (GalR1-3) in pain transmission remains unclear. In this study, a new agonist, M617, that preferentially binds to GalR1, a GalR2 agonist (AR-M1896), and a GalR2 antagonist (M871) were tested in the periphery to elucidate the role of peripheral GalR1 and GalR2 in nociception. Ipsilateral, but not contralateral, hindpaw injection of M617 reduced capsaicin (CAP)-induced flinching by similar to 50%, suggesting that GalR1 activation produces anti-nociception. This anti-nociceptive effect was blocked by intraplantar injection of the non-selective GalR antagonist M35. In contrast ipsilateral, but not contralateral, intraplantar injection of GalR2 agonist AR-M1896 enhanced the CAP-induced nociception (1.7-fold). The GalR2 antagonist M871 blocked the pro-nociceptive effect of AR-M1896 in a dose-dependent manner. This antagonist had no effect on nociceptive behaviors induced by CAP alone. The data demonstrate that activation of peripheral GalR1 results in anti-nociception but activation of peripheral GalR2 produces pro-nociception. Thus, the use of these pharmacological tools may help to elucidate the contribution of GalR subtypes in nociceptive processing, identifying potential drug targets for the treatment of peripheral pain. (c) 2006 Elsevier Inc. All rights reserved.