Peripheral CGRP release as a marker for neurogenic inflammation: a model system for the study of neuropeptide secretion in rat paw skin
Peripheral CGRP release as a marker for neurogenic inflammation: a model system for the study of neuropeptide secretion in rat paw skin
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DOI：
10.1016/s0304-3959(97)00108-5
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发表时间：
1997-11-01
期刊：
影响因子：
7.4
通讯作者：
Flores, CM
中科院分区：
文献类型：
--
作者：
Kilo, S;HardingRose, C;Flores, CM
外周中促炎性神经肽的局部释放与神经源性炎症的发展相关。然而，有越来越多的报告表明，这些神经肽参与的机制，在靶组织中启动和维持炎症反应的组织依赖性差异。由于皮肤经常参与组织损伤，本研究旨在开发一种模型，用于评估皮肤肽分泌作为皮肤组织中神经源性炎症的标志物。皮肤组织降钙素基因相关肽（CGRP）是已知参与神经源性炎症的几种神经肽之一，被选择来研究辣椒素对周围神经分泌的影响。用放射免疫分析法测定了大鼠后肢毛状皮肤的离体皮层表面灌流后，基础和辣椒素诱发的外周CGRP（iCGRP）的释放。这些研究的主要目的是表征这种释放的各种性质，包括剂量依赖性、胞吐作用和受体介导作用，以及辣椒素脱敏的急性和长期效应。辣椒素在3至300 μ M的浓度范围内显著且剂量依赖性地增加iCGRP的释放。省略钙离子或用竞争性辣椒素受体拮抗剂辣椒平处理完全抑制辣椒素诱导的iCGRP释放。用浓度范围为0.3至100 μ M的辣椒素进行调节刺激后，用100 μ M辣椒素对皮肤进行灌流，导致CGRP反应的急性剂量依赖性脱敏。此外，新生儿注射辣椒素后的慢性脱敏完全消除了对辣椒素的急性iCGRP反应。这里描述的方法应该被证明是一个有价值的工具，用于评估的过程调节外周，皮肤释放的促炎神经肽。因此，这种策略可能会导致更好地理解神经源性炎症，特别是皮肤中的神经源性炎症的发展和维持机制。(C)1997年国际疼痛研究协会。出版社：Elsevier Science B.V.
The local release of pro-inflammatory neuropeptides in the periphery has been associated with the development of neurogenic inflammation. However, there is an increasing number of reports demonstrating tissue-dependent differences regarding the mechanisms engaged by these neuropeptides to initiate and maintain the inflammatory response in the target tissue. Since skin is often involved in tissue injury, the present studies were designed to develop a model for assessing cutaneous peptide secretion as a marker for neurogenic inflammation in skin tissue. skin tissue. Calcitonin gene-related peptide (CGRP), as one of several neuropeptides known to be involved in neurogenic inflammation, was chosen to study capsaicin-induced effects on peripheral neurosecretion. The corial surface of the hairy skin of a rat hindlimb was superfused in vitro, and the basal and capsaicin-evoked peripheral release of immunoreactive CGRP (iCGRP) was measured using a radioimmunoassay, The main objectives of these studies were to characterize the various properties of this release including dose-dependency, exocytosis and receptor-mediation as well as the effects of acute and long-term capsaicin desensitization. Capsaicin significantly and dose-dependently increased the release of iCGRP at concentrations ranging from 3 to 300 mu M. Omission of calcium ions or treatment with the competitive capsaicin receptor antagonist capsazepine completely inhibited the capsaicin-induced iCGRP release. Superfusion of the skin with 100 mu M capsaicin following a conditioning stimulation with capsaicin at concentrations ranging from 0.3 to 100 mu M led to an acute, dose-dependent desensitization of the CGRP response. In addition, chronic desensitization following the neonatal injection of capsaicin completely abolished the acute iCGRP response to capsaicin. The method described here should prove to be a valuable tool for the evaluation of the processes regulating the peripheral, cutaneous release of pro-inflammatory neuropeptides. This strategy, therefore, may lead to a better understanding of the mechanisms involved in the development and maintenance of neurogenic inflammation, particularly in the skin. (C) 1997 International Association for the Study of Pain. Published by Elsevier Science B.V.