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Effect of calmodulin antagonists on calmodulin‐induced biphasic modulation of Ca 2+ ‐induced Ca 2+ release
Author(s) -
Ikemoto Takaaki,
Lino Masamitsu,
Endo Makoto
Publication year - 1996
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.1476-5381.1996.tb15455.x
Subject(s) - calmodulin , trifluoperazine , mastoparan , chemistry , calcium , antagonist , biophysics , chlorpromazine , endoplasmic reticulum , mechanism of action , long term potentiation , pharmacology , receptor , biochemistry , biology , g protein , in vitro , organic chemistry
1 Calmodulin (CaM) has a biphasic effect on Ca 2+ ‐induced Ca 2+ release (CICR) from the sarcoplasmic reticulum (SR): potentiation and inhibition at low (pCa > 6.0) and high (pCa 5) Ca 2+ concentrations, respectively. To characterize the mode of action of CaM, we studied the effect of CaM antagonists on the CICR in skinned muscle fibres of the rabbit. Ca 2+ release was measured by microfluorometry with Fura‐2. 2 A CaM antagonist, trifluoperazine (TFP), potentiated the CICR in a dose‐dependent manner (10–300 μ m ) at pCa 6, where a simple reversal of the CaM effect would be inhibition of the CICR. Furthermore, 100 μ m TFP sensitized the CICR to Ca 2+ . A similar effect was produced by other CaM antagonists that were tested: chlorpromazine, W‐7, mastoparan, and peptide fragment of CaM‐binding residues of CaM‐dependent protein kinase II. 3 The biphasic effect of CaM on the CICR was observed even in the presence of high concentrations of CaM antagonists or CaM‐binding peptides. 4 From these results we suggest that CaM has a unique mode of action on the CICR which is quite different from the effect of CaM on known enzymes.