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

Abstract

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 (A1R). 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 A1R, 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 A1R increased forskolin‐stimulated cAMP production instead of decreasing it. This alteration was not accompanied by changes in αG protein levels. The functionality of A1R 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 A1R coupling from Gi to Gs proteins. Finally, radioligand binding assays revealed that density and affinity of A1R were not significantly altered by HIS. In summary, the results obtained show that HIS induces long‐term changes in the A1R/AC signaling pathway in rat brain cortex.

Na+/K+- and Mg2+-ATPases and Their Interaction with AMPA, NMDA and D2 Dopamine Receptors in an Animal Model of Febrile Seizures

“…Moreover, although the mechanisms by which prolonged FS could contribute to epilepsy remains unknown, no cell death and neuronal circuit reorganization seems to be involved, suggesting changes in neuronal function as the main mechanism in the epileptogenic process during development [ 4 , 7 , 8 ]. In that sense, multiple works carried out in recent years have revealed that HIS evoke changes in metabotropic receptors, such as adenosine A 1 and A 2A receptors [ 9 , 10 , 11 , 12 , 13 ], metabotropic glutamate receptor [ 14 ] or GABA B receptor [ 15 ]. Ionotropic receptors, including NMDA and GABA A receptors, are also modulated by FS [ 16 , 17 , 18 , 19 ].…”