Characterization of capsaicin-induced, capsazepine-insensitive relaxation of ileal smooth muscle of rats
Characterization of capsaicin-induced, capsazepine-insensitive relaxation of ileal smooth muscle of rats
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DOI：
10.1016/j.ejphar.2004.01.014
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发表时间：
2004-03-08
影响因子：
5
通讯作者：
Mori, M
中科院分区：
文献类型：
--
作者：
Fujimoto, S;Mori, M
通过测量大鼠回肠纵向平滑肌中肌球蛋白 (MLC20) 20-kDa 调节轻链亚基的等长力和磷酸化，研究了辣椒素诱导的乙酰胆碱和 KCl 收缩松弛的机制。辣椒素以浓度依赖性方式松弛乙酰胆碱和 KCl 刺激的制剂；前者对辣椒素的敏感性低于后者，对辣椒素的最大反应（罂粟碱引起的松弛的百分比）分别为 70.6 +/- 7.5%，n = 10 和 97.1 +/- 0.9%，n = 13，P < 0.05。反应显示没有脱敏。与硝苯地平一样，辣椒素也可以放松用 L 型 Ca2+ 通道激动剂预收缩的组织。辣椒素的松弛作用不受辣椒西平（香草酸 VR1 受体的选择性拮抗剂）、硝基-L-精氨酸、吲哚美辛、胍乙啶或可溶性鸟苷酸环化酶抑制剂的抑制。在不含 Ca2+ 的 EGTA 溶液中，辣椒素可抑制乙酰胆碱诱导的短暂收缩。应用 10 muM 乙酰胆碱（7.8 +/- 2.0%，n = 6 vs. 22.6 +/- 3.2%，n = 6）和 65.9 mM KCl（2.2 +/- 0.3%，n = 8 vs. 10.7 +/-）后 1 分钟，MLC20 的磷酸化（磷酸化占总 MLC20 的百分比）增加1.7%，n = 12)。辣椒素比乙酰胆碱诱导的 MLC20 磷酸化增加更显着地减少 KCl 诱导的增加。当用乙酰胆碱使组织收缩20分钟时，MLC20磷酸化增加，辣椒素显着降低乙酰胆碱引起的收缩并消除MLC20磷酸化。表明辣椒素通过其对平滑肌的直接作用来放松大鼠回肠，并且辣椒素抑制涉及通过非L型Ca2+通道的细胞外Ca2+流入的收缩机制，可能通过储存操纵的Ca2+通道和从细胞内储存位点释放Ca2+。辣椒素对乙酰胆碱和 KCl 诱导的收缩的影响可以通过 MLC20 磷酸化的减少来解释。 (C) 2004 Elsevier B.V. 保留所有权利。
The mechanisms underlying the capsaicin-induced relaxation of the acetylcholine- as well as KCl-contraction were studied by measuring isometric force and phosphorylation of 20-kDa regulatory light chain subunit of myosin (MLC20) in ileal longitudinal smooth muscles of rats. Capsaicin relaxed acetylcholine- and KCl-stimulated preparations in a concentration-dependent manner; the former was less sensitive to capsaicin than the latter and maximum responses to capsaicin (a percentage of papaverine-induced relaxation) were 70.6 +/- 7.5%, n = 10 and 97.1 +/- 0.9%, n = 13, P < 0.05, respectively. The response showed no desensitization. Like nifedipine, capsaicin relaxed the tissue precontracted with an agonist of L-type Ca2+ channels as well. The relaxant effect of capsaicin was not inhibited by capsazepine (a selective antagonist of vanilloid VR1 receptors), nitro-L-arginine, indomethacin, guanethidine, nor by inhibitors of soluble guanylate cyclase. Capsaicin inhibited acetylcholine-induced transient contraction in a Ca2+-free, EGTA solution. Phosphorylation of MLC20 (a percentage of phosphorylated to total MLC20) was increased I min after application of 10 muM acetylcholine (7.8 +/- 2.0%, n = 6 vs. 22.6 +/- 3.2%, n = 6) and of 65.9 mM KCl (2.2 +/- 0.3%, n = 8 vs. 10.7 +/- 1.7%, n = 12). Capsaicin reduced the KCl-induced increase more markedly than acetylcholine-induced increase in MLC20 phosphorylation. When the tissue was contracted for 20 min with acetylcholine, MLC20 phosphorylation was increased, and capsaicin reduced markedly the contraction and abolished MLC20 phosphorylation both elicited by acetylcholine. It is suggested that capsaicin relaxes the rat ileum via its direct action on smooth muscle, and that capsaicin inhibits contractile mechanisms involving extracellular Ca2+ influx via non-L-type Ca2+ channels, possibly via store-operated Ca2+ channels and Ca2+ release from intracellular storage sites. The effects of capsaicin on acetylcholine- and KCl-induced contraction could be explained by a decrease in MLC20 phosphorylation. (C) 2004 Elsevier B.V. All rights reserved.