Repression of stimulated calcitonin gene-related peptide secretion by topiramate
Repression of stimulated calcitonin gene-related peptide secretion by topiramate
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DOI：
10.1111/j.1526-4610.2006.00538.x
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发表时间：
2006-09-01
期刊：
影响因子：
5
通讯作者：
Cady, Roger
中科院分区：
文献类型：
--
作者：
Durham, Paul L.;Niemann, Christine;Cady, Roger
客观。-这项拟议研究的目标是确定托吡酯对三叉神经节神经元基础和刺激释放降钙素基因相关肽（CGRP）的影响。背景。- CGRP与偏头痛有关。临床证据支持托吡酯作为一种有效的偏头痛预防药。在这项研究中，托吡酯和CGRP表达之间的联系进行了调查。利用大鼠三叉神经节的原代培养物来确定托吡酯对由去极化刺激（KCl）、一氧化氮和/或质子刺激的CGRP释放的影响。使用CGRP特异性放射免疫测定法测定分泌到培养基中的CGRP的量。用KCl、一氧化氮供体S-亚硝基-N-乙酰青霉胺或质子（pH 5.5培养基）处理三叉神经培养物导致CGRP释放量显著增加（3至5倍）。托吡酯治疗以时间和浓度依赖性方式抑制KCl刺激的CGRP释放。然而，托吡酯并没有改变三叉神经元释放的未受刺激或基础CGRP的量。此外，托吡酯抑制一氧化氮和质子介导的CGRP分泌。这些研究结果表明，托吡酯可以直接抑制三叉神经感觉神经元中CGRP的刺激释放。我们认为托吡酯预防偏头痛发作的能力可能与抑制三叉神经元CGRP分泌有关。
Objective.—The goal of the proposed research was to determine the effect of topiramate on basal and stimulated release of calcitonin gene‐related peptide (CGRP) from trigeminal ganglia neurons.Background.—CGRP is implicated in migraine headaches. Clinical evidence supports topiramate as an effective migraine prophylactic. In this study, the connection between topiramate and CGRP expression was investigated.Methods.—Primary cultures of rat trigeminal ganglia were utilized to determine the effects of topiramate on CGRP release stimulated by a depolarizing stimulus (KCl), nitric oxide, and/or protons. The amount of CGRP secreted into the culture media was determined using a CGRP‐specific radioimmunoassay.Results.—Treatment of trigeminal cultures with KCl, nitric oxide donor S‐nitroso‐N‐acetylpenicillamine, or protons (pH 5.5 media) caused a marked increase (3 to 5 fold) in the amount of CGRP release. Topiramate treatment repressed KCl‐stimulated CGRP release in a time‐ and concentration‐dependent manner. However, topiramate did not alter the amount of unstimulated or basal CGRP released from trigeminal neurons. In addition, topiramate inhibited nitric oxide and proton mediated CGRP secretion.Conclusions.—Findings from these studies demonstrate that topiramate can directly repress the stimulated release of CGRP from sensory trigeminal neurons. We propose that topiramate's ability to prevent migraine attacks may involve inhibition of CGRP secretion from trigeminal neurons.