Hyperthermia-induced seizures produce long-term effects on the functionality of adenosine A1 receptor in rat cerebral cortex.

Febrile seizures are one of the most frequent childhood neurological disorders; they are classified into simple and prolonged, depending on their duration. Prolonged FS lasts more than 15 min and may evoke neurological sequelae in a process in which molecular alterations seem to play an important role. Adenosine is a purine nucleoside that exerts anticonvulsant effects through binding to adenosine A1 receptor (A1 R). This receptor belongs to the GPCR superfamily and is negatively coupled to adenylyl cyclase (AC) activity through Gi proteins. In the present study, we analyzed the functionality of A1 R, measured as the inhibition of forskolin-stimulated AC activity, 48 hr after hyperthermia-induced seizures (HIS). Surprisingly, the results obtained show that the activation of A1 R increased forskolin-stimulated cAMP production instead of decreasing it. This alteration was not accompanied by changes in αG protein levels. The functionality of A1 R remained altered two months after HIS. However, this alteration was abolished when AC assays were carried out in the presence of anti αGs subunit-specific antibody, suggesting that HIS can switch A1 R coupling from Gi to Gs proteins. Finally, radioligand binding assays revealed that density and affinity of A1 R were not significantly altered by HIS. In summary, the results obtained show that HIS induces long-term changes in the A1 R/AC signaling pathway in rat brain cortex.