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.

中文翻译：

---

热疗诱发的癫痫发作对大鼠大脑皮层腺苷 A 1 受体的功能产生长期影响

热性惊厥是最常见的儿童神经系统疾病之一。它们根据持续时间分为简单和延长。长时间的 FS 持续超过 15 分钟，并可能在分子改变似乎起重要作用的过程中引起神经系统后遗症。腺苷是一种嘌呤核苷，通过与腺苷 A1 受体 (A1R) 结合发挥抗惊厥作用。该受体属于 GPCR 超家族，通过 Gi 蛋白与腺苷酸环化酶 (AC) 活性负耦合。在本研究中，我们分析了 A1R 的功能，测量为高热诱发癫痫发作 (HIS) 48 小时后毛喉素刺激的 AC 活性的抑制。令人惊讶的是，获得的结果表明 A1R 的激活增加了毛喉素刺激的 cAMP 产生，而不是减少了它。这种改变不伴随αG蛋白水平的变化。在 HIS 后两个月，A1R 的功能仍然改变。然而，当在抗 αGs 亚基特异性抗体存在的情况下进行 AC 测定时，这种改变被取消，表明 HIS 可以将 A1R 偶联从 Gi 转换为 Gs 蛋白。最后，放射性配体结合分析表明，HIS 没有显着改变 A1R 的密度和亲和力。总之，获得的结果表明 HIS 诱导大鼠大脑皮层中 A1R/AC 信号通路的长期变化。表明 HIS 可以将 A1R 偶联从 Gi 转换为 Gs 蛋白。最后，放射性配体结合分析表明，HIS 没有显着改变 A1R 的密度和亲和力。总之，获得的结果表明 HIS 诱导大鼠大脑皮层中 A1R/AC 信号通路的长期变化。表明 HIS 可以将 A1R 偶联从 Gi 转换为 Gs 蛋白。最后，放射性配体结合分析表明，HIS 没有显着改变 A1R 的密度和亲和力。总之，获得的结果表明 HIS 诱导大鼠大脑皮层中 A1R/AC 信号通路的长期变化。