Abstract
Ca2+/calmodulin protein kinase II (CaMK II) is enriched in the presynapse, where it is involved in the control of neurotransmitter release. Protein phosphorylation promoted by CaMK II was analyzed in crude subsynaptosomal fractions prepared from rats treated for two weeks with one of the three antidepressant agents paroxetine, fluvoxamine, venlafaxine. The fractions used were synaptosomal membranes (LP1), synaptic vesicles (LP2), and synaptic cytosol (LS2). We found a significant increase of phosphate incorporation in synaptic vesicles, as compared to controls, in the autophosphorylated α-subunit of CaMK II and in the two major substrates of the kinase, synapsin I and synaptotagmin. Increased phosphorylation, in the case of CaMK II, ranged from 170 to 270%, and was confirmed by immunoprecipitation of the phosphoprotein. This was solely due to increased phosphorylation, because quantitative immunoblot showed that total kinase amount was unchanged. As CaMK II and related substrates are involved in the regulation of neurotransmitter release, this result suggests a new site for the action of antidepressant agents.
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Popoli, M., Perez, J., Vocaturo, C. et al. Long-term treatment with antidepressant agents affects Ca2+/calmodulin protein kinase II in hippocampal presynapses. Neuropsychopharmacol 11, 263 (1994). https://doi.org/10.1038/sj.npp.1380126
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DOI: https://doi.org/10.1038/sj.npp.1380126