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. [Copyright &y& Elsevier]