Shiga K-i, Hirano K, Nishimura J, Niiro N, Naito S, Kanaide H
Division of Molecular Cardiology, Research Institute of Angiocardiology, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Br J Pharmacol. 2007 Aug;151(7):1014-24. doi: 10.1038/sj.bjp.0707317. Epub 2007 Jun 4.
The intravesical administration of dimethyl sulphoxide (DMSO) is used to alleviate the symptoms of interstitial cystitis. We investigated the relaxant effect of DMSO and its underlying mechanism in the detrusor muscle.
The effects of DMSO on contraction, on Ca2+ sensitivity of myofilaments, and on myosin light chain (MLC) phosphorylation were investigated in both intact and alpha-toxin-permeabilized strips of rabbit detrusor muscle.
In fura-PE3-loaded strips, DMSO (>1%) induced a significant relaxation during sustained contractions induced by 60 mM K+-depolarization or 10 microM carbachol, while having no effect on the Ca2+ level. DMSO decreased the level of MLC phosphorylation during the contractions induced by 60 mM K+ and 10 microM carbachol. DMSO also inhibited both the contraction and MLC phosphorylation induced by calyculin-A in intact strips. In the alpha-toxin-permeabilized preparations, DMSO relaxed the Ca2+-induced contraction and also inhibited the tension development induced by a stepwise increment of Ca2+ concentrations. Such a relaxant effect of DMSO was enhanced in the presence of phosphate.
DMSO relaxes rabbit detrusor muscle by decreasing the Ca2+ sensitivity of myofilaments. Inhibition of the kinase activities involved in myosin phosphorylation may play a major role in DMSO-induced Ca2+ desensitization. Inhibition of the cross-bridge cycling at the step of phosphate release may also contribute to the relaxant effect of DMSO. Such relaxant effects of DMSO could be linked to the therapeutic effect of DMSO in interstitial cystitis.
膀胱内灌注二甲基亚砜（DMSO）用于缓解间质性膀胱炎的症状。我们研究了DMSO对逼尿肌的舒张作用及其潜在机制。
在完整的和经α-毒素通透处理的兔逼尿肌条上，研究了DMSO对收缩、肌丝Ca²⁺敏感性以及肌球蛋白轻链（MLC）磷酸化的影响。
在负载fura-PE3的肌条中，DMSO（>1%）在由60 mM K⁺去极化或10 μM卡巴胆碱诱导的持续收缩过程中引起显著舒张，而对[Ca²⁺]i水平无影响。DMSO在由60 mM K⁺和10 μM卡巴胆碱诱导的收缩过程中降低了MLC磷酸化水平。DMSO还抑制了完整肌条中由Calyculin-A诱导的收缩和MLC磷酸化。在经α-毒素通透处理的标本中，DMSO使Ca²⁺诱导的收缩舒张，并抑制了由Ca²⁺浓度逐步增加诱导的张力发展。在磷酸盐存在的情况下，DMSO的这种舒张作用增强。
DMSO通过降低肌丝的Ca²⁺敏感性使兔逼尿肌舒张。抑制参与肌球蛋白磷酸化的激酶活性可能在DMSO诱导的Ca²⁺脱敏中起主要作用。在磷酸盐释放步骤抑制横桥循环也可能有助于DMSO的舒张作用。DMSO的这种舒张作用可能与DMSO在间质性膀胱炎中的治疗作用有关。
