Inhibition by SK&F 96365 of Ca2+ current, IL-2 production and activation in T lymphocytes.
1. By use of whole cell patch-clamp and Indo-1 fluorescence studies of the Jurkat T leukaemic cell line, we show that the new organic antagonist of receptor-mediated Ca2+ entry, SK&F 96365, inhibits the T cell Ca2+ current in a dose-dependent fashion, with an IC50 of 12 microM. 2. SK&F 96365 also inhibits [3H]-thymidine incorporation and interleukin-2 (IL-2) synthesis in peripheral blood lymphocytes. 3. SK&F 96365 has no effect on Ca2+ stores release or K+ channels. 4. This is the first account of an organic inhibitor of the T cell Ca2+ current. The ability of SK&F 96365 to inhibit IL-2 synthesis and cell proliferation suggests that a new class of related Ca2+ channel blockers can be developed as immunosuppressive agents.
Department of Molecular Pharmacology and Medicine, Stanford University School of Medicine, California 94305-5332.
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Chung
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McDonald
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Gardner
D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007093:Imidazoles; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015221:Potassium Channels; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium