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The activity of nitric oxide synthase (NOS) in rat parotid acinar cells was measured using a newly synthesized fluorescent NO indicator DAF-2/DA. Our results show that NO production is most effectively stimulated by activation of the beta-adrenergic receptor, and to a minor extent by substance P (SP). NO activates the production of cGMP, an intracellular messenger that has been shown to release Ca2+ from ryanodine-sensitive intracellular stores. We found that cGMP is also able to release Ca2+ from ryanodine-insensitive intracellular stores. Our data show that a rise in the cGMP concentration induces inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] synthesis and Ca2+ release from intracellular stores.
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