Neurotransmitter-stimulated breakdown of endogenous polyphosphoinositides in post mortem human brain

Elisabet Sarri, Fernando Picatoste, Enrique Claro

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Membranes from human brain cortex (8–12 h post mortem) were labelled with [3H]inositol, in the presence of CMP, through the back reaction catalysed by Ptdlns synthase. The enzyme incorporated [3H]inositol into phosphoinositides at a maximal rate of 419 pmol min−1 mg protein−1. In the absence of CMP, the labelling rate due to the Ptdlns headgroup exchanging enzyme was 36 pmol min−1 mg protein−1. Human brain Ptdlns synthase showed Kmapp values of 0.49 mM and 18 μM for inositol and CMP, respectively. In the presence of ATP, [3H]polyphosphoinositides formed after [3H]PtdIns were hydrolysed by phospholipase C in a GTPγS and neurotransmitter receptor agonist-dependent manner. Production of 3H-inositol phosphates as stimulated by GTPγS (350% of basal) was increased by the muscarinic agonists carbachol and oxotremorine-M (600% of basal) and by serotonin (485% of basal). The relative potencies of carbachol and oxotremorine-M were consistent with an action at muscarinic receptors. These results show that coupling between muscarinic and serotonin receptors and phospholipase C is preserved in membranes from post mortem human brain cortex and validate the use of a method involving direct [3H]inositol labelling of a membrane fraction to study the functional state of phospholipase C-coupled receptors in human brain samples. © Rapid Communications of Oxford Ltd.
Original languageEnglish
Pages (from-to)1059-1062
JournalNeuroReport
Volume5
DOIs
Publication statusPublished - 1 Jan 1994

Keywords

  • Human brain
  • Inositol phosphates
  • Muscarinic receptors
  • Phosphatidylinositol
  • Phosphoinositides
  • Phospholipase C
  • Serotonin receptors

Fingerprint Dive into the research topics of 'Neurotransmitter-stimulated breakdown of endogenous polyphosphoinositides in post mortem human brain'. Together they form a unique fingerprint.

Cite this