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 OX₃ receptors. We hypothesized that the activation of OX₁ receptors stimulated cAMP synthesis in primary rat astrocyte cultures.