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The effects of the immunosuppressants, tacrolimus (FK506) and cyclosporin A (CsA), on catecholamine (CA) release were examined in cultured bovine adrenal chromaffin cells.In intact cells, FK506 (1–30 μM) inhibited CA release stimulated by acetylcholine (ACh; 100 μM), 1,1-dimethyl-4-phenyl-piperazinium (DMPP, 10 μM) or high K+ (40 mM). CsA (1–30 μM) had a little inhibitory effect on the ACh- or DMPP-stimulated CA release, whereas it enhanced the high K+-stimulated CA release.In β-escin-permeabilized cells, FK506 inhibited CA release stimulated by Ca2+ (1 and 10 μM) in the presence and absence of MgATP (2 mM). CsA induced CA release under Ca2+-free condition and enhanced the Ca2+-stimulated CA release in the presence and absence of MgATP.It is known that the Ca2+-dependent exocytosis involves at least two distinct steps, ATP-requiring priming stage and ATP-independent fusion step in adrenal chromaffin cells. Therefore, it is suggested that FK506 inhibits the Ca2+-dependent exocytosis probably at the fusion step whereas CsA induces CA release from bovine adrenal chromaffin cells.