Dantrolene blocks the tonic contractions to carbachol and histamine with smaller effects on the phasic due to release of intracellular Ca2+ in ileal longitudinal muscle

Abstract

1. Dantrolene (10(-5)-10(-4) M) inhibited carbachol- or histamine-induced tonic response according to the decrease in Ca2+ uptake as determined by La method more than the phasic response in ileal muscle. However, dantrolene further reduced the second phasic response to sequential application of carbachol or histamine. 2. After saponin-treatment of the fibres, which leaves the Ca2+ storage sites intact, dantrolene had no effect on the IP3-induced contraction. 3. The results suggest that dantrolene inhibited the carbachol- or histamine-induced tonic response mainly by inhibiting Ca2+ influx through receptor operated Ca2+ channels in ileum with only slight effect on the intracellular Ca2+ release from the storage sites. However, when dantrolene was continuously present, dantrolene might reduce a part of the Ca2+ supply into the Ca2+ storage sites.