Effect of reboxetine treatment on brain cAMP- and calcium/calmodulin-dependent protein kinases.
Previous studies showed that the type II Ca(2+)/calmodulin- and cAMP-dependent protein kinases (CaMKII and PKA) are affected by long-term antidepressant treatment in presynaptic and somatodendritic compartments, respectively. This study describes the long-term effects of the selective noradrenaline reuptake inhibitor reboxetine on PKA and CaMKII, in both the microtubule and subsynaptosomal fractions of rat brain. Unlike other antidepressants, chronic reboxetine induced in the cerebrocortical soluble and microtubule fractions a decrease in the [(32)P]cAMP binding to the type II PKA regulatory subunit. No change in the cAMP-dependent endogenous phosphorylation of the protein substrate, microtubule-associated protein 2 was observed. In the hippocampal subsynaptosomal fractions (synaptic vesicles and synaptosomal membranes) reboxetine induced a robust increase in the activity but not in the expression of CaMKII. An increase in the calcium/calmodulin-dependent phosphorylation of presynaptic substrates was also detected. These findings showed that reboxetine modulates post-receptor signal transduction systems in rat brain.
Mori
S
S
Center of Neuropharmacology, Institute of Pharmacological Sciences, University of Milan, Milan, Italy.
Popoli
M
M
Brunello
N
N
Racagni
G
G
Perez
J
J
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000378:metabolism*; D002352:Carrier Proteins; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D002373:Cyclic AMP Receptor Protein / Q000378:metabolism; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009025:Morpholines / Q000008:administration & dosage*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077593:Reboxetine; D013347:Subcellular Fractions / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D013574:Synaptosomes / Q000737:chemistry / Q000201:enzymology
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D009025:Morpholines; D000077593:Reboxetine; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases