Synergistic activation of phosphoinositide hydrolysis induced in brain slices by norepinephrine and the excitatory amino acid agonist, Trans-ACPD

Krystyna Kolasa, R. S. Jope

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Norepinephrine and trans-1-aminocyclopentyl-1,3-dicarboxylic acid (ACPD) each individually stimulated hydrolysis of phosphoinositides and when tested in combination caused a stimulation that was 50-90% greater than additive in hippocampal and cortical slices of the rat but not in striatal slices. This synergistic augmentation of hydrolysis of phosphoinositide was evident with all stimulatory concentrations of norepinephrine and of ACPD up to 1 mM, at which point ACPD was inhibitory. A time-course study revealed no lag in the synergistic interaction and no down-regulation through 60 min of incubation of the augmented response to the combined agonists. The synergistic reaction was mediated by α1-adrenergic receptors and by metabotropic excitatory amino acid receptors. Increased intracellular calcium, but not activation of protein kinase C, may play a role in mediating the synergistic interaction. Thus, a unique synergistic stimulatory interaction was found between two receptors coupled with phosphoinositide metabolism, a finding which also supports the suggestion that these two systems are co-localized in some cells.

Original languageEnglish (US)
Pages (from-to)21-28
Number of pages8
JournalNeuropharmacology
Volume32
Issue number1
DOIs
StatePublished - Jan 1993
Externally publishedYes

Keywords

  • ACPD
  • excitatory amino acid
  • inositol
  • norepinephrine
  • phosphoinositide

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Fingerprint Dive into the research topics of 'Synergistic activation of phosphoinositide hydrolysis induced in brain slices by norepinephrine and the excitatory amino acid agonist, Trans-ACPD'. Together they form a unique fingerprint.

Cite this