CaMKII regulates amphetamine-induced ERK1/2 phosphorylation in striatal neurons.
Amphetamine activates extracellular signal-regulated kinase 1 and 2 (ERK1/2) resulting in cAMP response element-binding protein (CREB) and Elk-1 phosphorylation in striatal neurons. In the present study we investigated whether calcium and calmodulin-dependent protein kinase II (CaMKII) regulates amphetamine-induced ERK1/2 pathways in striatal neurons using Western blot and immunohistochemical analysis. Acute administration of amphetamine (5 mg/kg, i.p.) increased phosphorylated (p)CaMKII immunoreactivity. Inhibition of CaMKII by intrastriatal infusion of KN62 (2, 10, or 25 nmol) attenuated amphetamine-induced increases in pERK1/2, pCREB, and pElk-1 immunoreactivity in the ipsilateral dorsal striatum in a dose-dependent manner. These data suggest that CaMKII controls amphetamine-activated ERK1/2 pathways in striatal neurons in vivo.
Choe
Eun Sang
ES
Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, 2411 Holmes St., M3-C15, Kansas City, MO 64108, USA.
Wang
John Q
JQ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology*; D019969:Amphetamine-Related Disorders / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D050807:ets-Domain Protein Elk-1
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D015259:Dopamine Agents; C494114:Elk1 protein, rat; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000661:Amphetamine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D004298:Dopamine