title: Chloroquine, quinine and quinidine inhibit calcium release from macrophage intracellular stores by blocking inositol 1,4,5-trisphosphate binding to its receptor.
abstract: The binding of many ligands to cellular receptors induces a signaling cascade which generates inositol 1,4,5-trisphosphate (IP3). IP3 binding to its receptors in various internal compartments causes a rapid Ca2+ efflux into the cytosol. We now demonstrate that chloroquine blocks ligand-induced Ca2+ mobilization without affecting IP3 synthesis. The effect is independent of the ligand employed and occurred with five unrelated ligands; namely, alpha 2-macroglobulin-methylamine, angiotensin II, bradykinin, carbachol, and epidermal growth factor. Chloroquine, quinidine, and quinine, however, block binding of [3H]IP3 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.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: U K
authors.initials: UK
authors.lastname: Misra
authors.forename: G
authors.initials: G
authors.lastname: Gawdi
authors.forename: S V
authors.initials: SV
authors.lastname: Pizzo
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002451:Cell Compartmentation; D002738:Chloroquine / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D011802:Quinidine / Q000494:pharmacology*; D011803:Quinine / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
chemical_list: D000962:Antimalarials; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D002738:Chloroquine; D011803:Quinine; D011802:Quinidine; D002118:Calcium