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.

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