Analgesic effects of Tyr-W-MIF-1: a mixed mu2-opioid receptor agonist/mu1-opioid receptor antagonist.
Analgesic effects of Tyr-W-MIF-1: a mixed mu2-opioid receptor agonist/mu1-opioid receptor antagonist.
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Tyr-W-MIF-1 的镇痛作用：混合 mu2-阿片受体激动剂/mu1-阿片受体拮抗剂。
DOI：
10.1016/s0014-2999(96)00656-5
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发表时间：
1996
影响因子：
5
通讯作者：
Paul,D
中科院分区：
文献类型：
--
作者：
Gergen,KA;Zadina,JE;Paul,D
Tyr-W-MIF-1（Tyr-Pro-Trp-Gly-NH 2）是一种天然存在的神经肽，对μ-阿片受体具有高度选择性。最近，鞘内（i.t.）Tyr-W-MIF-1在小鼠中显示通过脊髓μ2-阿片受体介导的有效镇痛。在本研究中，我们研究了Tyr-W-MIF-1的脊髓上的镇痛作用，使用侧脑室（i. c. v.）在小鼠中施用。Tyr-W-MIF-1的镇痛作用呈剂量依赖性，其ED_（50）为31.4 μg，可被纳洛酮（ED_（50）= 4.46 nmol）和μ阿片受体拮抗剂β-funalcumamine拮抗，但不被μ阿片受体选择性拮抗剂纳洛嗪拮抗。I.T.然而，纳洛酮（ED 50 = 0.12 nmol）在拮抗i. c. v. Tyr-W-MIF-1诱导的镇痛方面比i. c. v.纳洛酮强近40倍。Tyr-W-MIF-1对脑内μ1阿片受体也有拮抗作用。静脉注射Tyr-W-MIF-1与静脉注射吗啡或静脉注射[d-Ala 2，MePhe 4，Gly（ol）5]脑啡肽（DAMGO）同时给药可显著降低对任一单独给药药物的镇痛反应。因此，Tyr-W-MIF-1在小鼠i. c. v.给药后作为混合μ2-阿片受体激动剂μ1-阿片受体拮抗剂发挥作用。
Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) is a naturally occurring neuropeptide that displays high selectivity for μ-opioid receptors. Recently, intrathecal (i.t.) Tyr-W-MIF-1 was shown to induce potent analgesia mediated through spinal μ2-opioid receptors in mice. In the current study, we investigated the supraspinal analgesic effects of Tyr-W-MIF-1 using intracerebroventricular (i.c.v.) administration in mice. I.c.v. Tyr-W-MIF-1 induced a dose-dependent analgesic response with an ED50of 31.4 μg that was antagonized by i.c.v. naloxone (ED50= 4.46 nmol) and the μ-opioid receptor antagonist β-funaltrexamine but not by the μ1-opioid receptor-selective antagonist naloxonazine. I.t. naloxone (ED50= 0.12 nmol), however, was nearly 40-fold more potent than i.c.v. naloxone at antagonizing i.c.v. Tyr-W-MIF-1-induced analgesia. Tyr-W-MIF-1 also possesses antagonist activity at μ1-opioid receptors in brain. Coadministration of i.c.v. Tyr-W-MIF-1 with i.c.v. morphine or i.c.v. [d-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO) significantly decreased the analgesic response to either drug administered alone. Thus, Tyr-W-MIF-1 functions as a mixed μ2-opioid receptor agonist μ1-opioid receptor antagonist after i.c.v. administration in mice.