Capsaicin-induced, capsazepine-insensitive relaxation of the guinea-pig ileum
Capsaicin-induced, capsazepine-insensitive relaxation of the guinea-pig ileum
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DOI：
10.1016/j.ejphar.2005.11.011
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发表时间：
2006-01-13
影响因子：
5
通讯作者：
Kunimatsu, M
中科院分区：
文献类型：
--
作者：
Fujimoto, S;Mori, M;Kunimatsu, M
通过测定豚鼠回肠纵行平滑肌的等长收缩力和肌球蛋白20 kDa调节轻链亚基（MLC 20）的磷酸化水平，研究了辣椒素引起的非瞬时受体电位香草酸受体1（TRPV 1）依赖性舒张的机制。在乙酰胆碱刺激的组织中，辣椒素（1-100 μ M）和树脂毒素（10 nM-1 μ M）产生浓度依赖性松弛。4-氨基吡啶和高浓度KCl溶液可减弱舒张反应，但辣椒平、四乙基铵、Ba ~（2+）、格列本脲、卡律巴毒素加蜂毒肽或大麻素受体I型拮抗剂和降钙素基因相关肽均不减弱舒张反应。RhoA激酶抑制剂在30 μ M时降低辣椒素的松弛作用。辣椒素和树脂毒素减少乙酰胆碱和咖啡因引起的短暂收缩在无钙，EGTA的解决方案。辣椒素在30 μ M的20分钟没有改变MLCo磷酸化的基础水平，但废除了MLC 20磷酸化的乙酰胆碱的增加。这表明，在使用的浓度辣椒素的舒张作用是不介导的TRPV 1，但4-氨基吡啶敏感的K+通道，辣椒素抑制收缩机制，涉及Ca 2+释放从细胞内存储网站。这种松弛可以通过MLC 20磷酸化的减少来解释。(c)2005 Elsevier BX保留所有权利。
The mechanisms underlying transient receptor potential vanilloid receptor type 1 (TRPV1)-independent relaxation elicited by capsaicin were studied by measuring isometric force and phosphorylation of 20-kDa regulatory light chain subunit of myosin (MLC20) in ileum longitudinal smooth muscles of guinea-pigs. In acetylcholine-stimulated tissues, capsaicin (1-100 mu M) and resiniferatoxin (10 nM-1 mu M) produced a concentration-dependent relaxation. The relaxant response was attenuated by 4-aminopyridine and high-KCl solution, but not by capsazepine, tetraethylammonium, Ba2+, glibenclamide, charybdotoxin plus apamin nor antagonists of cannabinoid receptor type I and calcitonin-gene related peptide. A RhoA kinase inhibitor reduced the relaxant effect of capsaicin at 30 mu M. Capsaicin and resiniferatoxin reduced acetylcholine- and caffeine-induced transient contractions in a Ca2+ -free, EGTA solution. Capsaicin at 30 mu M for 20 min did not alter basal levels of MLCo phosphorylation, but abolished an increase by acetylcholine in MLC20 phosphorylation. It is suggested that the relaxant effect of capsaicin at concentrations used is not mediated by TRPV 1, but by 4-aminopyridine-sensitive K+ channels, and that capsaicin inhibits contractile mechanisms involving Ca2+ release from intracellular storage sites. The relaxation could be explained by a decrease in phosphorylation of MLC20. (c) 2005 Elsevier BX All rights reserved.