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Kainic Acid Down-regulates NOP Receptor Density and Gene Expression in Human Neuroblastoma SH-SY5Y Cells

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Abstract

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 μM) for 3 h did not affect NOP receptor density. In contrast, a NOP B max down-regulation was detected in cells exposed to 10 μM 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.

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Abbreviations

N/OFQ:

nociceptin

CNQX:

6-cyano-7-nitroquinoxaline-2,3-dione

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Acknowledgement

The authors wish to thank Dr. Gabriele Campana for his helpful technical suggestions. This study was supported by grants from the Italian Ministry for the University and Scientific Research (PRIN 2006–2007).

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Authors and Affiliations

  1. Department of Pharmacology, University of Bologna, Irnerio 48, 40126, Bologna, Italy

    Rosalia Cannarsa, Daniela Landuzzi, Chiara Cavina, Sanzio Candeletti & Patrizia Romualdi

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  1. Rosalia Cannarsa
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  2. Daniela Landuzzi
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  3. Chiara Cavina
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  4. Sanzio Candeletti
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  5. Patrizia Romualdi
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Correspondence to Patrizia Romualdi.

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Cannarsa and Landuzzi contributed equally to this work.

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Cannarsa, R., Landuzzi, D., Cavina, C. et al. Kainic Acid Down-regulates NOP Receptor Density and Gene Expression in Human Neuroblastoma SH-SY5Y Cells. J Mol Neurosci 35, 171–177 (2008). https://doi.org/10.1007/s12031-008-9038-x

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  • DOI: https://doi.org/10.1007/s12031-008-9038-x

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