Abstract
The effects of cyclic ADP-ribose (cADPR) and the immunosuppressant drug FK506 on microsomal Ca 2+ release through a ryanodine-sensitive mechanism were investigated in rat pancreatic acinar cells. After a steady state of 45Ca 2+ uptake into the microsomal vesicles, ryanodine or caffeine was added. Preincubation of the vesicles with cADPR (0.5 μM) shifted the dose–response curve of ryanodine- or caffeine-induced 45Ca 2+ release from the vesicles to the left. Preincubation with cADPR shifted the dose–response curve of the FK506-induced 45Ca 2+ release upward. Preincubation with FK506 (3 μM) shifted the dose–response curve of the ryanodine- or caffeine-induced 45Ca 2+ release to the left by the same extent as that in the case of cADPR. FK506 shifted the dose–response curve of the cADPR-induced 45Ca 2+ release upward. The presence of both cADPR and FK506 enhanced the ryanodine (30 μM)- or caffeine (10 mM)-induced 45Ca 2+ release by the same extent as that in the case of cADPR alone or FK506 alone. These results indicate that cADPR and FK506 modulate the ryanodine-sensitive Ca 2+ release mechanism of rat pancreatic acinar cells by increasing the ryanodine or caffeine sensitivity to the mechanism. In addition, there is a possibility that the mechanisms of modulation by cADPR and FK506 are the same.
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