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Effects of verapamil on the response of the guinea‐pig tracheal muscle to carbachol
Author(s) -
Baba K.,
Satake T.,
Takagi K.,
Tomita T.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb10222.x
Subject(s) - carbachol , verapamil , chemistry , contraction (grammar) , gallopamil , calcium , medicine , endocrinology , muscle contraction , guinea pig , biophysics , biochemistry , biology , receptor , organic chemistry
1 The effects of verapamil on the contraction of the guinea‐pig tracheal smooth muscle induced by calcium (Ca 2+ ) or barium (Ba 2+ ) were investigated in three different conditions: (a) in excess K solution, (b) in the presence of carbachol, and (c) in excess K solution containing carbachol. In order to clarify the contractions, the effects of removal and readdition of the divalent cations were also investigated. 2 In Ca 2+ ‐loaded tissues, application of carbachol in Ca‐free medium produced a transient contraction, the magnitude of which decreased the longer the duration of exposure to Ca 2+ ‐free solution. 3 In Ca 2+ ‐depleted, Ba 2+ ‐loaded tissues, application of carbachol in a Ba 2+ ‐ and Ca 2+ ‐free medium produced a transient contraction the magnitude of which decreased the longer the duration of exposure to the Ba 2+ ‐ and Ca 2+ ‐free solution. 4 After exposure to Ca 2+ ‐free solution for 40 min, the sensitivity of the tissue to Ca 2+ was greater in the presence of 30 μM carbachol (ED 50 = 0.06 mM) than in the presence of 40 mM K + (ED50 = 0.3 mM). The Ca 2+ ‐sensitivity in the presence of 30 μM carbachol plus K + (40 mM) was not different from that in the presence of 30 μM carbachol alone. 5 In Ca 2+ ‐free solution, the sensitivity of the tissue to Ba 2+ in the presence of 40 mM K + (ED 50 = 1.4 mM) was not different from that observed in the presence of 30 μM carbachol (ED 50 = 1.3 mM). 6 After exposure to Ca 2+ ‐free solution, verapamil produced a parallel rightward shift in the concentration‐response curves to added Ca 2+ and Ba 2+ in the presence of either 40 mM K + , 30 μM carbachol or 40 mM K + plus 30 μM carbachol. 7 The pA 2 values of verapamil against Ca 2+ responses in the presence of 40 mM K + , 30 μM carbachol and 40 mM K + plus 30 μM carbachol were 7.0, 6.5 and 6.5, respectively. The pA 2 values of verapamil against Ba 2+ responses under these conditions were 7.1, 7.0 and 7.1, respectively. 8 It is concluded that the sustained contraction produced by carbachol requires the influx of Ca 2+ and that Ba 2+ can substitute for Ca 2+ in this process. Furthermore, the ionic channels which admit Ca 2+ may be modified by carbachol to different degrees depending on the presence of Ca 2+ or Ba 2+ . Such changes alter the affinity of the channel to verapamil.