Arachidonic acid regulates two Ca2+ entry pathways via nitric oxide

Abstract Several regulated Ca 2+ entry pathways have been identified, with capacitative Ca 2+ entry (CCE) being the most characterized. In the present study, we examined Ca 2+ entry pathways regulated by arachidonic acid (AA) in mouse parotid acini. AA induced Ca 2+ release from intracellular stores, and increased Ca 2+ entry. AA inhibited thapsigargin (Tg)-induced CCE, whereas AA activated Ca 2+ entry when CCE was blocked by gadolinium (Gd 3+ ). AA-induced Ca 2+ entry was associated with depletion of calcium from ryanodine-sensitive stores; both AA-induced Ca 2+ release and Ca 2+ entry were inhibited by tetracaine and the nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI). The nitric oxide (NO) donor, 1,2,3,4-ox-triazolium,5-amino-3-(3,4-dichlorophenyl)-chloride (GEA 3162), but not 8-bromo-cGMP, mimicked the effects of AA in inhibiting CCE. Results suggest that AA acts via nitric acid to inhibit the CCE pathway that is selective for Ca 2+ , and to activate a second Ca 2+ entry pathway that is dependent on depletion of Ca 2+ from ryanodine-sensitive stores.