INHIBITION BY SK-AND-F-96365 OF CA2-2 PRODUCTION AND ACTIVATION IN T-LYMPHOCYTES( CURRENT, IL)

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 antagon ist of receptor-mediated Ca2+ entry, SK&F 96365, inhibits the T cell C a2+ current in a dose-dependent fashion, with an IC50 of 12 mu M. 2 SK &F 96365 also inhibits [H-3]-thymidine incorporation and interleukin-2 (IL-2) synthesis in peripheral blood lymphocytes. 3 SK&96365 has no e ffect on Ca2+ stores release or K+ channels. 4 This is the first accou nt of an organic inhibitor of the T cell Ca2+ current. The ability of SK&F 96365 to inhibit 1L-2 synthesis and cell proliferation suggests t hat a new class of related Ca2+ channel blockers can be developed as i mmunosuppressive agents.