Intravenous Administration of Pyroglutamyl Apelin-13 Alleviates Murine Inflammatory Pain via the Kappa Opioid Receptor.
Intravenous Administration of Pyroglutamyl Apelin-13 Alleviates Murine Inflammatory Pain via the Kappa Opioid Receptor.
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静脉注射焦谷氨酰 Apelin-13 通过 Kappa 阿片受体减轻小鼠炎症性疼痛。
DOI：
10.3389/fnins.2020.00929
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发表时间：
2020
影响因子：
4.3
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Lv S;Zhang X;Feng Y;Zhou Y;Cui B;Yang Y;Wang X
Apelin是一种内源性神经肽，广泛分布于中枢神经系统和外周组织中。焦谷氨酰 apelin-13 [(pyr)apelin-13] 是人血浆中主要的 apelin 亚型。然而，外周 (pyr)apelin-13 在疼痛调节中的作用尚不清楚。本研究的目的是通过福尔马林试验研究外周注射 (pyr)apelin-13 对炎性疼痛的影响，并评估该影响的机制基础。结果显示，在小鼠福尔马林测试的第二阶段中，静脉注射 (pyr)apelin-13（10、20 mg/kg）可显着减少舔/咬时间。相反，静脉注射。注射apelin-13对此效果没有影响。肌内注射 (pyr)apelin-13 仅以 20 mg/kg 的剂量减少第二阶段的舔/咬时间。静脉注射的抗伤害作用(pyr)apelin-13 被 apelin 受体（APJ，血管紧张素 II 受体样 1）拮抗剂 apelin-13(F13A) 拮抗。 (pyr)apelin-13（静脉注射 20 mg/kg）显着上调前额皮质中的 Aplnr 和 Adcy2 基因表达，而 Fos 基因表达下调。静脉注射的抗伤害作用(pyr)apelin-13 被阿片受体拮抗剂纳洛酮和特异性 kappa 阿片受体 (KOR) 拮抗剂去甲二托菲明 (nor-BNI) 阻断。 (pyr)Apelin-13 上调小鼠前额叶皮层（而非纹状体）中的强啡肽和 KOR 基因表达和蛋白质水平。 (pyr)Apelin-13 不影响运动行为。我们的结果表明，静脉注射在炎症性疼痛小鼠模型中，注射 (pyr)apelin-13 可通过 KOR 诱导镇痛作用。
Apelin is an endogenous neuropeptide, which has wide distribution in central nervous system and peripheral tissues. Pyroglutamyl apelin-13 [(pyr)apelin-13] is the major apelin isoform in human plasma. However, the role of peripheral (pyr)apelin-13 in pain regulation is unknown. The aim of this study was to investigate the effect of the peripheral injection of (pyr)apelin-13 on inflammatory pain using the formalin test as well as to evaluate the mechanistic basis for the effect. Results showed intravenous (i.v.) injection of (pyr)apelin-13 (10, 20 mg/kg) to significantly decrease licking/biting time during the second phase of the mouse formalin test. In contrast, i.v. injection of apelin-13 had no influence on such effect. Intramuscular injection of (pyr)apelin-13 reduced licking/biting time during the second phase only at a dose of 20 mg/kg. The antinociception of i.v. (pyr)apelin-13 was antagonized by the apelin receptor (APJ, angiotensin II receptor-like 1) antagonist, apelin-13(F13A). (pyr)apelin-13 (i.v. 20 mg/kg) markedly upregulated Aplnr and Adcy2 gene expression in the prefrontal cortex, whereas Fos gene expression was downregulated. The antinociception of i.v. (pyr)apelin-13 was blocked by the opioid receptor antagonist naloxone and the specific kappa opioid receptor (KOR) antagonist nor-binaltorphimine (nor-BNI). (pyr)Apelin-13 upregulated the dynorphin and KOR gene expression and protein levels in the mouse prefrontal cortex, not in striatum. (pyr)Apelin-13 did not influence the motor behavior. Our results demonstrate that i.v. injection of (pyr)apelin-13 induces antinociception via the KOR in the inflammatory pain mouse model.
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影响因子：
3.3
作者：
Fan, Junming;Guang, Hui;Gong, Yongsheng
通讯作者：
Gong, Yongsheng
影响因子：
7.4
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Abbadie, C;Taylor, BK;Basbaum, AI
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影响因子：
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作者：
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DOI：
10.1016/s0167-4889(99)00114-7
发表时间：
1999-10-13
影响因子：
5.1
作者：
Habata, Y;Fujii, R;Fujino, M
通讯作者：
Fujino, M
影响因子：
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作者：
Lv, Shuangyu;Zhou, Yuchen;Wang, Xinchun
通讯作者：
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