Inhibitory effects of caffeine on Ca2+ influx and histamine secretion independent of cAMP in rat peritoneal mast cells.

1. Caffeine did not evoke Ca2+ mobilization and histamine secretion. 2. Caffeine, as well as other methylxanthines but not forskolin or 8 bromo-cAMP, inhibited Ca2+ responses from compound 48/80. 3. Evoked histamine secretion was severely reduced by caffeine but not by cAMP analogs. 4. In beta-escin-permeabilized cells, caffeine did not affect resting and IP3-stimulated 45Ca2+ release, but it inhibited Ca(2+)-induced histamine secretion. 5. These results indicate that caffeine inhibits Ca2+ influx and Ca2+ efficacy in the secretory apparatus independent of cAMP, resulting in the inhibition of secretagogs-evoked histamine secretion from rat mast cells.