کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2531190 1558910 2016 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Antinociception of spirocyclopiperazinium salt compound LXM-10-M targeting α7 nicotinic receptor and M4 muscarinic receptor and inhibiting CaMKIIα/CREB/CGRP signaling pathway in mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Antinociception of spirocyclopiperazinium salt compound LXM-10-M targeting α7 nicotinic receptor and M4 muscarinic receptor and inhibiting CaMKIIα/CREB/CGRP signaling pathway in mice
چکیده انگلیسی

The present study was designed to investigate the antinociception of spirocyclopiperazinium salt compound LXM-10-M (2,4-dimethyl-9-β-m-hydroxyphenylethyl-3-oxo-6, 9-diazaspiro [5.5] undecane chloride) in thermal and chemical pain models, and further to explore the molecular target and potential signal pathway. We assessed the antinociception of LXM-10-M in hot-plate test, formalin test and acetic acid writhing test in mice. The possible changes of calcium/calmodulin-dependent protein kinase IIα (CaMKIIα)/cAMP response element-binding protein (CREB)/calcitonin gene related peptide (CGRP) signaling pathway were detected by Western Blot in mice. Administration of LXM-10-M produced significant antinociception in hot-plate test, formalin test and acetic acid writhing test in mice, with no obvious toxicity. The antinociceptive effects were blocked by pretreatment with methyllycaconitine citrate (MLA, α7 nicotinic receptor antagonist) or tropicamide (TRO, M4 muscarinic receptor antagonist). Western blot analysis showed that the upregulations of p-CaMKIIα, p-CREB and CGRP in the spinal cord were reduced by LXM-10-M in chemical pain model in mice, and the effects were blocked by MLA or TRO pretreatment. This is the first paper to report that LXM-10-M exerted significant antinociception, which may be attributed to the activation of α7 nicotinic receptor and M4 muscarinic receptor and thereby triggering the inhibition of CaMKIIα/CREB/CGRP signaling pathway in mice.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 770, 5 January 2016, Pages 92–98
نویسندگان
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