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Blockade by calmodulin inhibitors of Ca 2+ channels in smooth muscle from rat vas deferens
Author(s) -
Nakazawa Ken,
Higo Katsuya,
Abe Kazuho,
Tanaka Yoshio,
Saito Hiroshi,
Matsuki Norio
Publication year - 1993
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.1476-5381.1993.tb13543.x
Subject(s) - trifluoperazine , calmodulin , vas deferens , chemistry , endocrinology , medicine , biophysics , calcium , biology
1 Effects of three compounds which are used as calmodulin inhibitors (trifluoperazine, W‐7 and calmidazolium) on Ca 2+ channels were investigated in smooth muscle from rat vas deferens. 2 All three calmodulin inhibitors relaxed the smooth muscle precontracted by a high concentration of KCl (63.7 m m ). The order of potency for the relaxation was trifluoperazine > W‐7 > calmidazolium. 3 In binding studies using a microsomal fraction of vas deferens, all these calmodulin inhibitors displaced specific [ 3 H]‐nimodipine binding. Trifluoperazine and W‐7 inhibited the binding at concentrations that relaxed the smooth muscle whereas calmidazolium inhibited at concentrations much lower than those necessary for muscle relaxation. 4 Ba 2+ current flowing through voltage‐gated Ca 2+ channels was measured under whole‐cell voltage‐clamp conditions in isolated smooth muscle cells. The Ba 2+ current was suppressed by the three calmodulin inhibitors in the concentration‐range where inhibition of [ 3 H]‐nimodipine binding was observed. Neither voltage‐dependence nor the inactivation time course of Ba 2+ current were affected by these compounds. 5 The results suggest that the calmodulin inhibitors directly block Ca 2+ channels in the smooth muscle cells. The channel inhibition by trifluoperazine and W‐7, but perhaps not that by calmidazolium, may be responsible for the muscle relaxation observed with these compounds.