Cannarsa Rosalia, Landuzzi Daniela, Cavina Chiara, Candeletti Sanzio, Romualdi Patrizia
Department of Pharmacology, University of Bologna, Irnerio 48, 40126, Bologna, Italy.
J Mol Neurosci. 2008 Jun;35(2):171-7. doi: 10.1007/s12031-008-9038-x. Epub 2008 Feb 20.
Nociceptin (N/OFQ) is involved in neuronal excitability and in certain types of seizures. Kainate-induced seizures are associated with increased N/OFQ release in the rat thalamus and hippocampus, causing down-regulation of the N/OFQ receptor (NOP). In this study, we used the neuroblastoma SH-SY5Y cell line as a model to investigate the effects of kainate on NOP receptor density and gene expression. Exposure to kainate (10-50 microM) for 3 h did not affect NOP receptor density. In contrast, a NOP Bmax down-regulation was detected in cells exposed to 10 microM kainate for both 6 and 24 h. Moreover, our data show that kainate causes a decrease in NOP mRNA levels after 3, 6, and 24 h, an effect blocked by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). These findings show that kainate is able to affect the NOP system, both at biosynthesis and receptor density levels in SH-SY5Y cells, and that the kainate ionotropic receptor can contribute to the regulation of the NOP receptor. These data are in agreement with data obtained in vivo and provide new evidence concerning the existence of a cross-talk between NOP and kainate receptors, leading to an interplay between glutamate and N/OFQ circuits.
孤啡肽（N/OFQ）参与神经元兴奋性及某些类型的癫痫发作。在大鼠丘脑和海马中，海藻酸诱导的癫痫发作与N/OFQ释放增加有关，导致孤啡肽受体（NOP）下调。在本研究中，我们使用神经母细胞瘤SH-SY5Y细胞系作为模型，研究海藻酸对NOP受体密度和基因表达的影响。用10 - 50微摩尔的海藻酸处理3小时不影响NOP受体密度。相反，在暴露于10微摩尔海藻酸6小时和24小时的细胞中检测到NOP最大结合容量（Bmax）下调。此外，我们的数据表明，海藻酸在处理3小时、6小时和24小时后会导致NOP mRNA水平降低，这种效应被AMPA/海藻酸受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）阻断。这些发现表明，海藻酸能够在生物合成和受体密度水平上影响SH-SY5Y细胞中的NOP系统，并且离子型海藻酸受体可能参与NOP受体的调节。这些数据与体内获得的数据一致，并为NOP和海藻酸受体之间存在相互作用提供了新证据，这种相互作用导致谷氨酸和N/OFQ回路之间的相互影响。
