Arachidonic acid mobilizes Ca2+ from the endoplasmic reticulum and an acidic store in rat pancreatic β cells

Abstract

In rat pancreatic β cells, arachidonic acid (AA) triggered intracellular Ca2+ release. This effect could be mimicked by eicosatetraynoic acid, indicating that AA metabolism is not required. The AA-mediated Ca2+ signal was not affected by inhibition of ryanodine receptors or emptying of ryanodine-sensitive store but was reduced by ∼70% following the disruption of acidic stores (treatment with bafilomycin A1 or glycyl-phenylalanyl-β-naphthylamide (GPN)). The action of AA did not involve TRPM2 channels or NAADP receptors because intracellular dialysis of adenosine diphosphoribose (ADPR; an activator of TRPM2 channels) or NAADP did not affect the AA response. In contrast, stimulation of IP3 receptors via intracellular dialysis of adenophostin A, or exogenous application of ATP largely abolished the AA-mediated Ca2+ signal. Intracellular dialysis of heparin abolished the ATP-mediated Ca2+ signal but not the AA response, suggesting that the action of AA did not involve the IP3-binding site. Treatment with the SERCA pump inhibitor, thapsigargin, reduced the amplitude of the AA-mediated Ca2+ signal by ∼70%. Overall, our finding suggests that AA mobilizes Ca2+ from the endoplasmic reticulum as well as an acidic store and both stores could be depleted by IP3 receptor agonist. The possibility of secretory granules as targets of AA is discussed.