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Effect of calcium on phenothiazine inhibition of neutrophil degranulation
Author(s) -
Blackwood R. Alexander,
Hessler Ronald J.
Publication year - 1995
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.58.1.114
Subject(s) - degranulation , calmodulin , exocytosis , phenothiazine , liposome , biology , in vitro , annexin , chlorpromazine , calcium , microbiology and biotechnology , biochemistry , pharmacology , membrane , biophysics , chemistry , enzyme , receptor , organic chemistry
The phenothiazines are known to be potent inhibitors of calmodulin and have been used as probes for examining calmodulin‐dependent cellular functions. We report here that the characteristics of phenothiazine inhibition of exocytosis in neutrophils more closely resemble their interaction with the annexins in vitro. Ca 2+ ‐ dependent aggregation of liposomes mediated by either annexin I or annexin II was inhibited by the phenothiazines. Inhibition of liposome aggregation was not caused by interference with the binding of annexins to phospholipids. Rather, the phenothiazines increased the concentration of Ca 2+ required for aggregation. Likewise, in neutrophils pepneabilized with streptolysin O, inhibition of degranulation by phenothiazines could be overcome by increasing [Ca 2+ ]. These results suggest that inhibition by phenothiazines of neutrophil degranulation is secondary to the ability of these compounds to inhibit membrane‐membrane contact promoted by the annexins. J. Leukoc. Biol. 58: 114–118; 1995.