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Chloroquine, quinine and quinidine inhibit calcium release from macrophage intracellular stores by blocking inositol 1,4,5‐trisphosphate binding to its receptor
Author(s) -
Misra Uma Kant,
Gawdi Govind,
Pizzo Salvatore V.
Publication year - 1997
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(199702)64:2<225::aid-jcb6>3.0.co;2-z
Subject(s) - inositol trisphosphate , receptor , quinidine , inositol , chemistry , inositol trisphosphate receptor , pharmacology , chloroquine , biochemistry , biophysics , biology , immunology , malaria
The binding of many ligands to cellular receptors induces a signaling cascade which generates inositol 1,4,5‐trisphosphate (IP 3 ). IP 3 binding to its receptors in various internal compartments causes a rapid Ca 2+ efflux into the cytosol. We now demonstrate that chloroquine blocks ligand‐induced Ca 2+ mobilization without affecting IP 3 synthesis. The effect is independent of the ligand employed and occurred with five unrelated ligands; namely, α 2 ‐macroglobulin‐methylamine, angiotensin II, bradykinin, carbachol, and epidermal growth factor. Chloroquine, quinidine, and quinine, however, block binding of [ 3 H]IP 3 to its receptors by 90%, 88%, and 71%, respectively. These observations suggest a previously undetected mechanism by which these agents may in part function as antimalarials. J. Cell. Biochem. 64:225–232. © 1997 Wiley‐Liss, Inc.