Kainic acid down-regulates NOP receptor density and gene expression in human neuroblastoma SH-SY5Y cells.
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.
Cannarsa
Rosalia
R
Department of Pharmacology, University of Bologna, Irnerio 48, 40126, Bologna, Italy.
Landuzzi
Daniela
D
Cavina
Chiara
C
Candeletti
Sanzio
S
Romualdi
Patrizia
P
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology*; D009447:Neuroblastoma; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology; D018092:Kainic Acid Receptors / Q000378:metabolism; D011957:Receptors, Opioid / Q000235:genetics* / Q000378:metabolism*; D014316:Tritium; D000094942:Nociceptin Receptor
D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid; D007608:Kainic Acid; D018092:Kainic Acid Receptors; D011957:Receptors, Opioid; D014316:Tritium; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human