Activation of orexin/hypocretin type 1 receptors stimulates cAMP synthesis in primary cultures of rat astrocytes

The effects of orexins, which are also named hypocretins, on cAMP formation were examined in primary cultures of rat astrocytes. Orexin A, an agonist of OX1 and OX2 receptors, stimulated cAMP production with an EC50 value of 0.68 µM and potentiated the forskolin-induced increase in the nucleotide synthesis. [Ala11-D-Leu15]orexin B, an agonist of OX2 receptors, was inactive. The effects of orexin A were antagonized by SB 408124, a selective blocker of OX1 receptors, but were not affected by TCS OX2 29, a selective antagonist of OX2 receptors. We hypothesized that the activation of OX1 receptors stimulated cAMP synthesis in primary rat astrocyte cultures.