Dantrolene blocks the tonic contraction and calcium influx evoked by K+ in ileal longitudinal smooth muscle.
1. Dantrolene (10(-5)-10(-4) M) reduced the K+ (60 mM) tonic response in accordance with decreased Ca2+ uptake, as determined by La method, more than the phasic in ileal muscle. 2. After saponin-treatment of the fibers, which leaves the Ca2+ storage sites intact, dantrolene had only a slight effect on the caffeine-induced contraction. In Triton-X-100-treated fibers, in which the Ca2+ release sites are destroyed, dantrolene did not affect the Ca(2+)-induced contraction. 3. The results suggest that dantrolene inhibited the high-K(+)-induced tonic response mainly by inhibiting Ca2+ influx via voltage-dependent Ca2+ channels in ileum without affecting contractile elements. In contrast, dantrolene had only a slight effect on the intracellular Ca2+ release from caffeine-sensitive release sites.
Nasu
T
T
Department of Veterinary Pharmacology, Faculty of Agriculture, Yamaguchi University, Japan.
Oosako
H
H
Shibata
H
H
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology*; D016257:Fura-2; D006168:Guinea Pigs; D007082:Ileum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D017830:Octoxynol / Q000494:pharmacology; D011188:Potassium / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D000697:Central Nervous System Stimulants; D009125:Muscle Relaxants, Central; D012503:Saponins; D013501:Surface-Active Agents; D002110:Caffeine; D017830:Octoxynol; D003620:Dantrolene; D011188:Potassium; D002118:Calcium; D016257:Fura-2