Modifications in brain cAMP- and calcium/calmodulin-dependent protein kinases induced by treatment with S-adenosylmethionine

S. Zanotti, S. Mori, R. Radaelli, J. Perez, G. Racagni, M. Popoli

Research output: Contribution to journalArticlepeer-review

Abstract

Several lines of evidence suggest that the mechanism of action of antidepressant drugs (AD) involves adaptive changes occurring in intraneuronal post-receptor signal transduction cascades. Protein phosphorylation has a key role in signal transduction and was previously found to be a target in the action of AD (5-HT and/or NA reuptake blockers). Several studies showed that cAMP- and type II Ca2+/calmodulin-dependent protein kinases (PKA and CaMKII) are markedly affected by typical AD in two different and complementary cellular districts, respectively microtubules (a somatodendritic compartment) and synaptic vesicles (a presynaptic terminal compartment). In order to investigate whether the effect on protein kinases may be involved in the therapeutic action of drugs it is interesting to compare the effect of atypical AD with that of typical drugs. In this study the effect of the atypical AD S-adenosylmethionine (SAMe) was tested. Repeated (12 days) SAMe treatment induced in cerebrocortical microtubules an increase in the binding of cAMP to the RII PKA regulatory subunit and an increase in the endogenous phosphorylation of microtubule-associated protein 2, an effect resembling that of typical AD. In synaptic terminals the treatment induced an increase in the activity of CaMKII and in the endogenous phosphorylation of vesicular substrates. However, this modification was found in the cerebral cortex rather than in the hippocampus, where typical AD affect CaMKII. In addition the synapsin I level was decreased in the hippocampus and increased in the cerebral cortex, an effect not detected with typical AD. Copyright (C) 1998 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)1081-1089
Number of pages9
JournalNeuropharmacology
Volume37
Issue number8
DOIs
Publication statusPublished - Aug 1998

Keywords

  • Antidepressant
  • Neurotransmitter release
  • Protein phosphorylation
  • S-adenosylmethionine
  • Signal transduction
  • Synapsin I

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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