Misoprostol elevates intracellular calcium in Neuro-2a cells via protein kinase A

Misoprostol, a prostaglandin type E analogue, has been implicated in a number of neurodevelopmental disorders. However, its mode of action in the nervous system is not well understood. Misoprostol acts on the same receptors as prostaglandin E(2) (PGE(2)), a natural lipid-derived compound, which mediates important physiological functions in the nervous system via activation of four EP receptors (EP1-4). In this study we use a ratiometric calcium imaging with fura-2 AM as a calcium indicator to show that misoprostol alters intracellular calcium levels in mouse neuroblastoma (Neuro-2a) cells via similar mechanisms as PGE(2). We demonstrate that the misoprostol-induced increase in calcium is mediated by a protein kinase A (PKA)-dependent mechanism and that the EP4 receptor signaling pathway may play an inhibitory role on calcium regulation. Overall, this study provides further support for the involvement of PGE(2) signaling in calcium homeostasis and suggests its important role in the nervous system.