GAP-43 phosphorylation by PKC in rat cerebrocortical synaptosomes: effect of antidepressants.
Recent evidence, including our previous work, indicates that changes in both c-AMP and phospholipid-dependent protein kinases (PKA and PKC) may be involved in neuroadaptive mechanisms occurring in brain after repeated administration of antidepressants. The purpose of this study was to examine the phosphorylation of a major PKC substrate involved in modulation of neurotransmitter release, GAP-43, in a synaptosomal preparation from rat cerebral cortex after repeated administration of fluxetine (FL) and desipramine (DMI). Groups of male rats were treated for 21 days with either FL (5 mg/kg/day, i.p.), DMI (10 mg/kg/day, i.p.) or vehicle (controls) and cortical synaptosomes were prepared 48 h or 24 h after the last injection. Synaptosomal membrane proteins were resolved by SDS-PAGE. Western immunoblotting and immunoprecipitation with anti-GAP-43 antibody have identified the GAP-43 protein as a single distinct band of apparent molecular weight of 56 kDa. The extent of phosphorylation of GAP-43 protein by native PKC in synaptosomes of rats treated with either FL or DMI was not significantly different from that observed in control animals. The previously observed suppression of basal PKC activity in rat cortical synaptosomes by FL and DMI treatment was thus not reflected in altered GAP-43 phosphorylation. It is thus unlikely that changes in GAP-43 phosphorylation are involved in antidepressant-induced modulation of 5-HT release.
Li
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Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Hrdina
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PD
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D003891:Desipramine / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005473:Fluoxetine / Q000494:pharmacology; D019922:GAP-43 Protein; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000032:analysis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure
D000928:Antidepressive Agents; D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D005473:Fluoxetine; D012701:Serotonin; D011493:Protein Kinase C; D003891:Desipramine