Inhibition by SK&F 96365 of Ca²⁺ current, IL‐2 production and activation in T lymphocytes

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 μm. SK&F 96365 also inhibits [³H]‐thymidine incorporation and interleukin‐2 (IL‐2) synthesis in peripheral blood lymphocytes. SK&F 96365 has no effect on Ca²⁺ stores release or K⁺ channels. 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. 1994 British Pharmacological Society