Department of Biochemistry, Faculty of Pharmacy, Ege University, 35100 Bornova, Izmir, Turkey.
Epilepsy Res. 2013 Jul;105(1-2):13-9. doi: 10.1016/j.eplepsyres.2012.12.008. Epub 2013 Jan 18.
The opioid/nociceptin receptors are involved in many neurological disorders such as Alzheimer's disease, Parkinson's disease and epilepsy. Kainic acid (KA) is an analog of the excitatory amino acid transmitter glutamate and the systemic administration of KA induces status epilepticus (SE) in rodents. In this study, we examined the alterations in the G-protein activity and the gene expression levels of mu, kappa, delta opioid and nociceptin receptors (MOPr, KOPr, DOPr and NOPr) as well as PNOC, the precursor polypeptide of nociceptin-OFQ (N/OFQ) in KA-induced seizures in the rat brain cortex. KA was used to create seizures with the dose of 10 mg/kg body weight i.p. Following the KA administration, the rats were observed for 3 h to assess seizure activity. Seizures occurred approximately 45 min after the KA injection. Only rats exhibiting full limbic seizures, forelimb clonus with rearing, were used in this study. All animals were decapitated 4 h after the administration of KA. Our [(35)S]GTPγS binding results showed that there was a significant difference in both the affinity and efficacy particularly one of NOPr stimulation following KA treatment. Slight, but significant increase was observed for MOPr. Moreover PNOC, NOPr and MOPr mRNA levels were increased by KA treatment but there were no significant changes in the levels of DOPr and KOPr mRNAs. These results show that the activities of opioid/nociceptin receptors can be modified by KA-treatment, and MOPr, PNOC and NOPr are the most responsive to KA-induced seizures in the rat brain cortex.
阿片/孤啡肽受体参与许多神经紊乱，如阿尔茨海默病、帕金森病和癫痫。海人酸（KA）是兴奋性氨基酸递质谷氨酸的类似物，系统给予 KA 可在啮齿动物中诱导癫痫持续状态（SE）。在这项研究中，我们检查了 G 蛋白活性的改变和 mu、kappa、delta 阿片和孤啡肽受体（MOPr、KOPr、DOPr 和 NOPr）以及 PNOC（孤啡肽-OFQ（N/OFQ）的前体多肽）的基因表达水平，在 KA 诱导的大鼠大脑皮层癫痫发作中。KA 用于以 10 mg/kg 体重的剂量腹腔内给药以引发癫痫。在给予 KA 后，观察大鼠 3 小时以评估癫痫发作活动。癫痫发作大约在 KA 注射后 45 分钟发生。只有表现出全面边缘性癫痫发作、前肢阵挛伴站立的大鼠才用于本研究。KA 给药后 4 小时，所有动物均断头。我们的 [(35)S]GTPγS 结合结果表明，KA 处理后，特别是 NOPr 刺激的亲和力和效力存在显著差异。MOPr 略有但显著增加。此外，KA 处理增加了 PNOC、NOPr 和 MOPr 的 mRNA 水平，但 DOPr 和 KOPr 的 mRNA 水平没有显著变化。这些结果表明，阿片/孤啡肽受体的活性可通过 KA 处理进行修饰，并且 MOPr、PNOC 和 NOPr 对大鼠大脑皮层中 KA 诱导的癫痫发作最敏感。
