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Effects of semotiadil fumarate, a novel Ca 2+ antagonist, on cytosolic Ca 2+ level and force of contraction in porcine coronary arteries
Author(s) -
Kageyama Masaaki,
Yanagisawa Teruyuki,
Taira Norio
Publication year - 1995
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.1476-5381.1995.tb13345.x
Subject(s) - contraction (grammar) , antagonist , cytosol , muscle contraction , chemistry , calcium , biophysics , medicine , endocrinology , biochemistry , receptor , biology , enzyme , organic chemistry
1 The mechanisms of action of semotiadil fumarate, a novel Ca 2+ antagonist, were examined by measuring the cytosolic Ca 2+ level ([Ca 2+ ] i ) and force of contraction in porcine coronary arteries, and by determining [ 3 H]‐pyrilamine binding to bovine cerebellar membranes. 2 Semotiadil or verapamil (0.1 and 1 μ m ) inhibited both the high KCl‐induced increases in [Ca 2+ ] i and force in a concentration‐dependent manner. 3 Histamine (30 μ m ) produced transient increases followed by sustained increases in [Ca 2+ ] i and force, which were inhibited by semotiadil and verapamil (1 and 10 μ m ).& The agents were different in that semotiadil reduced the maximum [Ca 2+ ] i and force responses to histamine, but not pD 2 values, whereas verapamil did reduce the pD 2 values for histamine, but not the maximum responses. 4 Verapamil (10 μ m ), but not semotiadil, inhibited histamine‐induced increases in [Ca 2+ ] i and force in Ca 2+ ‐free solution. Neither semotiadil nor verapamil affected the increases in [Ca 2+ ] i and force induced by caffeine. Semotiadil even at the higher concentration (10 μ m ) did not displace specific binding of [ 3 H]‐pyrilamine to bovine cerebellar membranes. 5 These results suggest that semotiadil inhibits both KCl‐ and histamine‐induced contractions mainly by blocking voltage‐dependent L‐type Ca 2+ channels.