Nociception activates Elk-1 and Sap1a following expression of the ORL1 receptor in Chinese hamster ovary cells.
Nociceptin stimulation of the ORL1 receptor expressed in Chinese hamster ovary (CHO) cells results in the activation of the extracellular signal regulated kinases ERK1 and ERK2. ERK1/ERK2 activation is inhibited by pertussis toxin, the MEK inhibitor PD 98059 and by transient expression of alpha-transducin, indicating that ORL1 up-regulation of these kinases occurs as a consequence of the release of the G-protein betagamma complex following the activation of pertussis-toxin sensitive Galphai-family G-proteins. Using specific reporter genes we demonstrate that the transcription factors Elk-1 and Sapla are activated in a pertussis toxin-sensitive manner as a consequence of ORL1 upregulation of ERK1/ERK2 to induce changes in gene expression. The activation of these transcription factors is also inhibited following treatment with PD 98059 and following coexpression of alpha-transducin.
Receptor Systems Unit, Glaxo Wellcome Research and Development, Hertfordshire, UK.
N
N
Bevan
S
S
Scott
P E
PE
Shaw
M G
MG
Lee
F H
FH
Marshall
S
S
Rees
D000818:Animals; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009292:Narcotic Antagonists; D009619:Nociceptors / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011957:Receptors, Opioid / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors; D015293:Transducin / Q000096:biosynthesis; D015854:Up-Regulation; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4; D000094942:Nociceptin Receptor
D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; C494193:ELK4 protein, human; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D009292:Narcotic Antagonists; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D011957:Receptors, Opioid; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4; D000242:Cyclic AMP; D020794:Receptor Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D015293:Transducin; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000094942:Nociceptin Receptor