Differential effects of benzodiazepines on phospholipid methylation in hippocampus and cerebellum of rats

Maria Teresa Tacconi, Mario Salmona

Research output: Contribution to journalArticlepeer-review

Abstract

To elucidate the relationship between the occupancy of BDZ binding sites and phospholipid methylation in brain, we examined phosphatidylethanolamine-N-methyltransferase (PEMT) activity in synaptosomes of rat hippocampi and cerebella in the presence of BDZ ligands with different modes of action. We found that Ro 5-4864, a specific ligand for "peripheral type" receptors, increased PL methylation in hippocampal and cerebellar synaptosomes. This effect was directly related to receptor occupancy, since the specific antagonist PK lll95 inhibited the rise in PEMT activity induced by Ro 5-4864. Clonazepam, on the other hand, tended to reduce PL production in cerebellum and hippocampus except for hippocampal (3H)-phosphatidyl-N-monomethylethanolamine which was elevated by 40 to 70% at doses ranging from 10-9 to 10-6M. When equimolar concentrations of the antagonist Ro 15-1788 were given in association the clonazepam-induced phosphatidyl-N-monomethylethanolamine increase was reduced by 70%. These data support the involvement of structural and functional membrane alterations in the action of BDZ.

Original languageEnglish
Pages (from-to)525-531
Number of pages7
JournalLife Sciences
Volume42
Issue number5
DOIs
Publication statusPublished - 1988

ASJC Scopus subject areas

  • Pharmacology

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