Cyclic AMP induces ryanodine-sensitive Ca2+ release from microsomal vesicles of rat parotid acinar cells

The effect of cAMP on a ryanodine-sensitive Ca2+ release from microsomal vesicles of rat parotid acinar cells was studied. After a steady state of ATP-dependent 45Ca2+ uptake into the vesicles, cAMP was added to the medium with thapsigargin (TG) to block a reuptake of 45Ca2+. The addition of cAMP (1.0 mM) with TG released about 10% of the 45Ca2+ that had been taken up. The cAMP-induced 45Ca2+ release was strongly inhibited by pretreatment of the vesicles with 500 microMM ryanodine. Preincubation with cAMP (1 mM) abolished ryanodine (10 microM)-induced 45Ca2+ release. The presence of a specific inhibitor of cAMP-dependent protein kinase (PKA) H-89 (10 microMM) inhibited the cAMP-induced 45Ca2+ release. These results indicate that in rat parotid acinar cells, cAMP can activate a ryanodine-sensitive Ca2+ release mechanism in the endoplasmic reticulum and that this activation is via a PKA-dependent process.