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 E2 (PGE2), 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 PGE2. 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 PGE2 signaling in calcium homeostasis and suggests its important role in the nervous system.

Research highlights
► Misoprostol and PGE2 increase cytosolic calcium level in Neuro-2a cells.
► Misoprostol- and PGE2-induced elevation of calcium occurs via PKA-dependent mechanism.
► EP4/PI3K pathway plays an inhibitory role in calcium regulation in Neura-2a cells.