Dimethyl sulphoxide relaxes rabbit detrusor muscle by decreasing the Ca 2+ sensitivity of the contractile apparatus

Abstract

Background and purpose: 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. Experimental approach: The effects of DMSO on contraction, on Ca 2+ sensitivity of myofilaments, and on myosin light chain (MLC) phosphorylation were investigated in both intact and α-toxin-permeabilized strips of rabbit detrusor muscle. Key results: In fura-PE3-loaded strips, DMSO (>1%) induced a significant relaxation during sustained contractions induced by 60 mM K +-depolarization or 10 μM carbachol, while having no effect on the [Ca 2+] i level. DMSO decreased the level of MLC phosphorylation during the contractions induced by 60 mM K + and 10 μM carbachol. DMSO also inhibited both the contraction and MLC phosphorylation induced by calyculin-A in intact strips. In the α-toxin-permeabilized preparations, DMSO relaxed the Ca 2+-induced contraction and also inhibited the tension development induced by a stepwise increment of Ca 2+ concentrations. Such a relaxant effect of DMSO was enhanced in the presence of phosphate. Conclusions and implications: DMSO relaxes rabbit detrusor muscle by decreasing the Ca 2+ sensitivity of myofilaments. Inhibition of the kinase activities involved in myosin phosphorylation may play a major role in DMSO-induced Ca 2+ 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. © 2007 Nature Publishing Group All rights reserved.