The Signaling Pathways Involved in the Anticonvulsive Effects of the Adenosine A₁ Receptor

Adenosine acts as an endogenous anticonvulsant and seizure terminator in the brain. Many of its anticonvulsive effects are mediated through the activation of the adenosine A₁ receptor, a G protein-coupled receptor with a wide array of targets. Activating A₁ receptors is an effective approach to suppress seizures. This review gives an overview of the neuronal targets of the adenosine A₁ receptor focusing in particular on signaling pathways resulting in neuronal inhibition. These include direct interactions of G protein subunits, the adenyl cyclase pathway and the phospholipase C pathway, which all mediate neuronal hyperpolarization and suppression of synaptic transmission. Additionally, the contribution of the guanyl cyclase and mitogen-activated protein kinase cascades to the seizure-suppressing effects of A₁ receptor activation are discussed. This review ends with the cautionary note that chronic activation of the A₁ receptor might have detrimental effects, which will need to be avoided when pursuing A₁ receptor-based epilepsy therapies.