Antidepressants activate CaMKII in neuron cell body by Thr286 phosphorylation.
CaM kinase II, a regulator of synaptic plasticity, is implicated in pathophysiology and pharmacology of psychiatric disorders. Chronic treatment with antidepressants desipramine and reboxetine up-regulated CaM kinase II in neuronal cell bodies of hippocampus. mRNA/protein expression for alphaCaM kinase II was unchanged, whereas Thr phosphorylation was increased in pyramidal/granular cell bodies, suggesting that increased phosphorylation is responsible for kinase activation. Short-term treatment of neuronal cultures with reboxetine reduced kinase activation in a concentration-dependent manner. The short-term inhibitory effect of reboxetine suggests that kinase up-regulation during antidepressant drug treatment is an adaptive response compensating for initial functional down-regulation.
Tiraboschi
Ettore
E
Center of Neuropharmacology-Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milano, Via Balzaretti 9, 20133 Milano, Italy.
Giambelli
Roberto
R
D'Urso
Giordano
G
Galietta
Antonio
A
Barbon
Alessandro
A
de Bartolomeis
Andrea
A
Gennarelli
Massimo
M
Barlati
Sergio
S
Racagni
Giorgio
G
Popoli
Maurizio
M
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003891:Desipramine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009025:Morpholines / Q000008:administration & dosage; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077593:Reboxetine; D013912:Threonine / Q000378:metabolism*; D013997:Time Factors
D000928:Antidepressive Agents; D009025:Morpholines; D012333:RNA, Messenger; D013912:Threonine; D000077593:Reboxetine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium; D003891:Desipramine