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

Neuroscience. 2000;101(3):607-17. doi: 10.1016/s0306-4522(00)00379-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / analogs & derivatives
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Animals
  • Cyclic AMP Response Element-Binding Protein / drug effects
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • DNA-Binding Proteins*
  • Dizocilpine Maleate / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Imidazoles / pharmacology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Male
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism*
  • Neostriatum / drug effects
  • Neostriatum / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins / drug effects
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-fos / drug effects
  • Proto-Oncogene Proteins c-fos / metabolism
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Sodium Channels / drug effects
  • Sodium Channels / metabolism
  • Tetrodotoxin / pharmacology
  • Thionucleotides / pharmacology
  • Transcription Factors*
  • ets-Domain Protein Elk-1
  • p38 Mitogen-Activated Protein Kinases

Substances

  • 8-bromoadenosine-3',5'-cyclic monophosphorothioate
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Elk1 protein, rat
  • Enzyme Inhibitors
  • Flavonoids
  • Imidazoles
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-fos
  • Pyridines
  • Receptors, N-Methyl-D-Aspartate
  • Sodium Channels
  • Thionucleotides
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Tetrodotoxin
  • Dizocilpine Maleate
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one