1986 Fiscal Year Final Research Report Summary
Simultaneous assay of Calcium antagonistic and other antispsmodic activities of smooth muscle relaxants by "Ca reversal" phenomenon.
| Project/Area Number |
60571062
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Meiji College of Pharmacy |
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Principal Investigator |
UCHIDA Masaatsu Meiji College of Pharmacy, Department of Molecular Pharmacology, 薬学部, 教授 (90097197)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUO Naoe Meiji College of Pharmacy, Department of Molecular Pharmacology
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| Project Period (FY) |
1985 – 1986
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| Keywords | Calcium antagonist / antispasmodics / Calcium ion / Calcium reversal / inhibition / Uterus / smooth muscle / オキシトシン |
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| Research Abstract |
Ca ion, which is well known as a trigger of physiological responses may also act as an inhibitor of responses in lower concentrations than those act as triggers in rat uterine smooth muscle. Addition of resting level of Ca ion ( <10^(-8)> - <10^(-7)> M) reversed the contraction by oxytocin of uterine smooth muscle in Ca free solution after preincubation with 3mM EGTA for 1hr. This relaxation by Ca ion was named "Calcium reversal". This finding suggests that Ca ion at low concentrations has an inhibitory action. Ca reversal is manifested in the presence of Ca antagonists. So we tested availability of this phenomenon for the assay of Ca antagonistic activity. It was found that the system is very simple as the judgement is all or none and it is very useful because other antispasmodic actions can be determined simultaneously. <ED_(50)> values for Ca reversal of various drugs show their Ca antagonistic activity. The ratios of <ED_(50)> values for <10^(-4)> M Ca ion and for 3x <10^(-4)> M Ca ions represent selectivity of a drug for Ca channels. Further, the ratio in high <K^+> solution clearly shows the selectivity of a Ca antagonist for voltage-operated Ca channels. Thus this system is very useful for the assay of Ca antagonistic activities, which are very important for drug therapy.
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