Chloroquine, quinine and quinidine inhibit calcium release from macrophage intracellular stores by blocking inositol 1,4,5-trisphosphate binding to its receptor
✍ Scribed by Uma Kant Misra; Govind Gawdi; Salvatore V. Pizzo
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 110 KB
- Volume
- 64
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
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 21 efflux into the cytosol. We now demonstrate that chloroquine blocks ligand-induced Ca 21 mobilization without affecting IP 3 synthesis. The effect is independent of the ligand employed and occurred with five unrelated ligands; namely, a 2 -macroglobulinmethylamine, 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.