Inhibitory effect of somatostatin on prostaglandin E₂ synthesis by primary neonatal rat glial cells

Glial inflammation plays an integral role in the development of neurodegenerative disease. Although somatostatin is known to be a local anti-inflammatory factor in the periphery, evidence of a similar function in the brain is scarce. The aim of the present study was to investigate the effect of somatostatin on prostaglandin E₂ synthesis in primary neonatal rat glial cells. The data shows that high concentrations of somatostatin (10^{- 5}-10^{- 4}) significantly increased prostaglandin synthesis. By contrast, when used at physiologically relevant concentrations (10^{- 9}-10^{- 7} M), somatostatin and somatostatin receptor agonists decreased prostaglandin E₂ synthesis in non-stimulated glial cells as well as in lipopolysaccharide-induced prostaglandin synthesis. The inhibitory effect of somatostatin in lipopolysaccharide-treated cells could be mimicked by protein kinase A inhibitor and was prevented by forskolin. These observations suggest the presence of a novel neuro-immune feedback pathway through which somatostatin inhibits glial prostaglandin synthesis, and thus may prove to play a role in brain inflammation. This action of somatostatin may have a therapeutic potential in pathological conditions of the brain, where an inflammatory response is involved.