The Signaling Pathways Involved in the Anticonvulsive Effects of the Adenosine A(1) 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 A(1) receptor, a G protein-coupled receptor with a wide array of targets. Activating A(1) receptors is an effective approach to suppress seizures. This review gives an overview of the neuronal targets of the adenosine A(1) 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 A(1) receptor activation are discussed. This review ends with the cautionary note that chronic activation of the A(1) receptor might have detrimental effects, which will need to be avoided when pursuing A(1) receptor-based epilepsy therapies.