"Ca reversal": inhibition by submicromolar Ca2+ concentrations of contraction of smooth muscle and its use for assay of Ca channel blockers.
1. Ca ion, which is a trigger of many physiological responses, also acts as an inhibitor of responses at lower concentrations than those that act as triggers in rat uterine smooth muscle. 2. The contraction induced by oxytocin of uterine smooth muscle that had been preincubated in Ca-free solution with 3 mM EGTA for 1 hr was reversed by addition of a resting level of Ca ion (10(-8) - 10(-7) M). 3. This relaxation by Ca ion was named "Ca reversal". 4. This finding suggests that Ca ion at low concentrations has an inhibitory action. 5. Since Ca reversal is manifested in the presence of Ca antagonists, we tested the availability of this phenomenon for assay of Ca antagonistic activity. 6. This system is very simple because the judgement is all or none, and it is very useful because other antispasmodic actions can be determined simultaneously. 7. The ED50 values of various drugs for Ca reversal show their Ca antagonistic activities. 8. Furthermore, the value in high K+ solution shows the selectivity of a Ca antagonist for voltage-operated Ca channels. 9. Thus this system is very useful for assay of Ca antagonistic activities, which are very important for drug therapy in a wide variety of diseases.
Uchida
M K
MK
Department of Molecular Pharmacology, Meiji College of Pharmacy, Tokyo, Japan.
Sakai
K
K
Matsuo
K
K
D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*
D002121:Calcium Channel Blockers; D002118:Calcium