Effects of dantrolene and its derivatives on Ca(2+) release from the sarcoplasmic reticulum of mouse skeletal muscle fibres

British Journal of Pharmacology
Takaaki IkemotoM Endo

Abstract

1. We analysed the effect of dantrolene (Dan) and five newly synthesized derivatives (GIFs) on Ca(2+) release from the sarcoplasmic reticulum (SR) of mouse skeletal muscle. 2. In intact muscles, GIF-0185 reduced the size of twitch contraction induced by electrical stimulation to the same extent as Dan. GIF-0082, an azido-functionalized Dan derivative, also inhibited twitch contraction, although the extent of inhibition was less than that of Dan and of GIF-0185. 3. In skinned fibres, Dan inhibited Ca(2+)-induced Ca(2+) release (CICR) under Mg(2+)-free conditions at room temperature. In contrast, GIF-0082 and GIF-0185 showed no inhibitory effect on CICR under the same conditions. 4. Dan-induced inhibition of CICR was not affected by the presence of GIF-0082, whereas it was diminished in the presence of GIF-0185. 5. GIF-0082 and GIF-0185 significantly inhibited clofibric acid (Clof)-induced Ca(2+) release, as did Dan. 6. Several Dan derivatives other than GIF-0082 and GIF-0185 showed an inhibitory effect on twitch tension but not on the CICR mechanism. All of these derivatives inhibited Clof-induced Ca(2+) release. 7. The magnitudes of inhibition of Clof-induced Ca(2+) release by all Dan derivatives were well correlated with those...Continue Reading

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Citations

Jun 6, 2009·American Journal of Physiology. Cell Physiology·Gregory N FilatovMark M Rich
Mar 20, 2013·BioMed Research International·R A Bannister
Apr 27, 2016·The Journal of General Physiology·Josefina Ramos-Franco, Michael Fill
Apr 3, 2003·The American Journal of Emergency Medicine·Shaun L GreeneMary Kerins
Dec 4, 2003·Journal of Pharmacological Sciences·Ryotaku InoueMakoto Endo
Oct 1, 2009·Physiological Reviews·Makoto Endo
Jun 26, 2015·The Journal of Physiology·Nadège ZanouPhilippe Gailly
Feb 11, 2020·Brain : a Journal of Neurology·Joery P MolenaarDamien Sternberg

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