N-Methyl-D-aspartate receptors and p38 mitogen-activated protein kinase are required for cAMP-dependent cyclase response element binding protein and Elk-1 phosphorylation in the striatum.
In vivo cyclic adenosine monophosphate (cAMP)-induced N-methyl-D-aspartate receptor and mitogen-activated protein kinase activation was investigated in the dorsal striatum by semiquantitative immunocytochemistry. Intracerebroventricular infusion of 8-bromo-adenosine 3',5'-cyclic monophosphorothioate, Sp isomer (Sp-8-Br-cAMPS), increased phosphorylated cAMP-responsive element binding protein, phosphorylated Elk-1 and Fos immunoreactivity in a dose-dependent manner. Intracerebroventricular infusion of the N-methyl-D-aspartate antagonist, MK801, decreased, but tetrodotoxin or the mitogen-activated extracellular-regulated kinase inhibitor, PD98059, did not affect Sp-8-Br-cAMPS-induced phosphorylated c-AMP-responsive element binding protein, phosphorylated Elk-1, phosphorylated extracellular-signal-regulated kinase and Fos immunoreactivity. The p38 mitogen-activated protein kinase inhibitor, SB203580, decreased the Sp-8-Br-cAMPS-induced increase in all markers, except phosphorylated extracellular-signal-regulated kinase, in a dose-dependent manner. We suggest that N-methyl-D-aspartate receptors couple c-AMP to phosphorylation events and immediate early gene induction in the nucleus of striatal medium spiny neurons. These events are mediated by crosstalk between protein kinase A and mitogen-activated protein kinase cascades in vivo.
Choe
E S
ES
Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, NC 27858, USA.
McGinty
J F
JF
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D048051:p38 Mitogen-Activated Protein Kinases
C105593:8-bromoadenosine-3',5'-cyclic monophosphorothioate; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C494114:Elk1 protein, rat; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D013873:Thionucleotides; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013779:Tetrodotoxin; D016291:Dizocilpine Maleate; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one