Substance P1-7 induces antihyperalgesia in diabetic mice through a mechanism involving the naloxone-sensitive sigma receptors
Substance P1-7 induces antihyperalgesia in diabetic mice through a mechanism involving the naloxone-sensitive sigma receptors
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DOI：
10.1016/j.ejphar.2009.10.006
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发表时间：
2010-01-25
影响因子：
5
通讯作者：
Kamei, Junzo
中科院分区：
文献类型：
--
作者：
Carlsson, Anna;Ohsawa, Masahiro;Kamei, Junzo
我们最近利用大鼠爪水疱模型探索了速激素物质P神经活性片段物质P1-7在介导抗炎作用中的作用（Wiktelius et al., 2006）。我们观察到这种七肽对p物质诱导的反应具有剂量依赖性的抑制作用，这种抑制作用可被非选择性阿片受体拮抗剂纳洛酮逆转。在本研究中，我们检测了物质P1-7对链脲佐菌素诱导的糖尿病小鼠的抗痛觉作用的能力。我们发现P物质片段在糖尿病小鼠中产生强烈的剂量依赖性抗痛觉过敏。这种作用被纳洛酮逆转，但被选择性阿片受体拮抗剂-富纳曲胺、纳曲多或非二萘多非明逆转。分别对-、-或-阿片受体具有选择性。此外，物质P1-7诱导的抗痛觉作用被sigma(1)受体激动剂(+)-pentazocine部分逆转。但没有a受体拮抗剂BD1047（[2-（3,4-二氯苯基）乙基]- n -甲基-2-（二氨基）乙胺），表明纳洛酮敏感的西格玛受体参与了SP相关七肽的作用。这些结果表明，糖尿病小鼠的痛觉过敏可能部分是由于脊髓内源性sigma(1)受体系统的增强。(C) 2009 Elsevier B.V.版权所有
We have recently explored the role of the tachykinin substance P neuroactive fragment substance P1-7 in the mediation of anti-inflammatory effects using a blister model in the rat paw (Wiktelius et al., 2006). We observed that this heptapeptide induced a dose-dependent inhibitory effect on the substance P-induced response, which was reversible by the non-selective opioid receptor antagonist naloxone. In the present study, we examined the ability of substance P1-7 to induce antihyperalgesic effects in streptozotocin-induced diabetic mice. We found that the substance P fragment strongly and dose-dependently produced antihyperalgesia in diabetic mice. This effect was reversed by naloxone but not by the selective opioid receptor antagonist beta-funaltrexamine, naltrindole or nor-binaltorphimine. selective for the mu-, delta- or kappa-Opioid receptor, respectively. In addition, the anti hyperalgesic effect induced by substance P1-7 was partly reversed by a sigma(1) receptor agonist (+)-pentazocine. but not a a, receptor antagonist BD1047 ([2-(3,4-dichlorophenyl) ethyl]-N-methyl-2-(diamino)ethylamine), suggesting that involvement of the naloxone-sensitive sigma-receptor for the action of the SP related heptapeptides. These results suggest that hyperalgesia in diabetic mice may be, in part, due to the enhanced endogenous sigma(1) receptor systems in the spinal cord. (C) 2009 Elsevier B.V. All rights reserved.