Arachidonic acid regulates two Ca2+ entry pathways via nitric oxide.
Several regulated Ca2+ entry pathways have been identified, with capacitative Ca2+ entry (CCE) being the most characterized. In the present study, we examined Ca2+ entry pathways regulated by arachidonic acid (AA) in mouse parotid acini. AA induced Ca2+ release from intracellular stores, and increased Ca2+ entry. AA inhibited thapsigargin (Tg)-induced CCE, whereas AA activated Ca2+ entry when CCE was blocked by gadolinium (Gd3+). AA-induced Ca2+ entry was associated with depletion of calcium from ryanodine-sensitive stores; both AA-induced Ca2+ release and Ca2+ 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 Ca2+, and to activate a second Ca2+ entry pathway that is dependent on depletion of Ca2+ from ryanodine-sensitive stores.
Watson
Eileen L
EL
Department of Oral Biology, University of Washington, Seattle, WA 98195, USA. ewatson@u.washington.edu
Jacobson
Kerry L
KL
Singh
Jean C
JC
DiJulio
Dennis H
DH
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016257:Fura-2 / Q000737:chemistry; D005682:Gadolinium / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D010306:Parotid Gland / Q000378:metabolism*; D012433:Ryanodine / Q000494:pharmacology; D013748:Tetracaine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007191:Indazoles; D014230:Triazoles; D013748:Tetracaine; D012433:Ryanodine; D016718:Arachidonic Acid; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D019284:Thapsigargin; C082874:GEA 3162; D005682:Gadolinium; D006152:Cyclic GMP; D002118:Calcium; D016257:Fura-2; C080122:7-nitroindazole