caa a22 4500 463254740 CHVBK 20180405153351.0 cr unu---uuuuu 170326e20070701xx s 000 0 eng 10.1007/s10571-007-9151-3 doi (NATIONALLICENCE)springer-10.1007/s10571-007-9151-3 Glucocorticoids plus opioids up-regulate genes that influence neuronal function [Elektronische Daten] [Gregg Ward, Steven Franklin, Tonya Gerald, Krystal Dempsey, Darrel Clodfelter Jr., Dan Krissinger, Kruti Patel, Kent Vrana, Allyn Howlett] (1) This study investigated the functional genomics of glucocorticoid and opioid receptor stimulation in cellular adaptations using a cultured neuronal cell model. (2) Human SH-SY5Y neuroblastoma cells grown in hormone-depleted serum were treated for 2-days with the glucocorticoid receptor-II agonist dexamethasone (30nM); the μ-opioid receptor agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin acetate (DAMGO; 1nM); or dexamethasone (30nM) plus DAMGO (1nM). RNA was extracted; purified, reverse transcribed, and labeled cDNA was hybridized to a 10,000-oliogonucleotide-array human gene chip. Gene expression changes that were significantly different between treatment groups and were of interest due to biological function were verified by real-time reverse transcription polymerase chain reaction (RT-PCR). Five relevant genes were identified for which the combination of dexamethasone plus DAMGO, but neither one alone, significantly up-regulated gene expression (ANOVA, P<0.05). (3) Proteins coded by the identified genes: FRS2 (fibroblast growth factor receptor substrate-2; CTNNB1 (β1-catenin); PRCP (prolyl-carboxypeptidase); MPHOSPH9 (M-phase phosphoprotein 9); and ZFP95 (zinc finger protein 95) serve important neuronal functions in signal transduction, synapse formation, neuronal growth and development, or transcription regulation. Neither opioid, glucocorticoid nor combined treatments significantly altered the cell growth rate determined by cell counts and protein. (4) We conclude that sustained μ-opioid receptor stimulation accompanied by glucocorticoids can synergistically regulate genes that influence neuronal function. Future studies are warranted to determine if combined influences of glucocorticoid fluctuations and opioid receptor stimulation in vivo can orchestrate exagerated neuroadaptation to reinforcing drugs under chronic mild stress conditions. Springer Science+Business Media, LLC, 2007 Dexamethasone nationallicence DAMGO nationallicence Glucocorticoid receptors nationallicence Mu-opioid receptors nationallicence SH-SY5Y human neuroblastoma nationallicence Real-time reverse transcription-polymerase chain reaction nationallicence Synaptic plasticity nationallicence Ward Gregg Neuroscience of Drug Abuse Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 27707, Durham, NC, USA aut Franklin Steven Neuroscience of Drug Abuse Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 27707, Durham, NC, USA aut Gerald Tonya Neuroscience of Drug Abuse Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 27707, Durham, NC, USA aut Dempsey Krystal Neuroscience of Drug Abuse Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 27707, Durham, NC, USA aut Clodfelter Jr. Darrel Neuroscience of Drug Abuse Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 27707, Durham, NC, USA aut Krissinger Dan Department of Pharmacology, Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center, 17033, Hershey, PA, USA aut Patel Kruti Department of Pharmacology, Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center, 17033, Hershey, PA, USA aut Vrana Kent Department of Pharmacology, Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center, 17033, Hershey, PA, USA aut Howlett Allyn Neuroscience of Drug Abuse Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 27707, Durham, NC, USA aut Cellular and Molecular Neurobiology Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 27/5(2007-07-01), 651-660 0272-4340 27:5<651 2007 27 10571 https://doi.org/10.1007/s10571-007-9151-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10571-007-9151-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ward Gregg Neuroscience of Drug Abuse Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 27707, Durham, NC, USA aut NATIONALLICENCE 700 1- Franklin Steven Neuroscience of Drug Abuse Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 27707, Durham, NC, USA aut NATIONALLICENCE 700 1- Gerald Tonya Neuroscience of Drug Abuse Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 27707, Durham, NC, USA aut NATIONALLICENCE 700 1- Dempsey Krystal Neuroscience of Drug Abuse Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 27707, Durham, NC, USA aut NATIONALLICENCE 700 1- Clodfelter Jr Darrel Neuroscience of Drug Abuse Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 27707, Durham, NC, USA aut NATIONALLICENCE 700 1- Krissinger Dan Department of Pharmacology, Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center, 17033, Hershey, PA, USA aut NATIONALLICENCE 700 1- Patel Kruti Department of Pharmacology, Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center, 17033, Hershey, PA, USA aut NATIONALLICENCE 700 1- Vrana Kent Department of Pharmacology, Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center, 17033, Hershey, PA, USA aut NATIONALLICENCE 700 1- Howlett Allyn Neuroscience of Drug Abuse Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 27707, Durham, NC, USA aut NATIONALLICENCE 773 0- Cellular and Molecular Neurobiology Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 27/5(2007-07-01), 651-660 0272-4340 27:5<651 2007 27 10571 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer