D-aspartate activates mGlu receptors coupled to polyphosphoinositide hydrolysis in neonate rat brain slices

Neurosci Lett. 2010 Jul 12;478(3):128-30. doi: 10.1016/j.neulet.2010.04.077. Epub 2010 May 7.

Abstract

The D-amino acid, D-aspartate, is abundant in the developing brain, yet its function is unknown. Addition of d-aspartate to hippocampal or cortical slices prepared from 8- to 9-day-old rats stimulated polyphosphoinositide (PI) hydrolysis to a slightly greater extent than L-glutamate. The action of D-aspartate was concentration-dependent with an apparent EC(50) value of 1 mM and a maximal stimulation of 6- and 20-fold in cortical and hippocampal slices, respectively. Stimulation of PI hydrolysis by D-aspartate was largely reduced by pharmacological blockade of mGlu5 metabotropic glutamate receptors with 2-methyl-6-(phenylethynyl)pyridine. These findings suggest that D-aspartate behaves as an endogenous agonist of mGlu5 receptors during early postnatal life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain / drug effects
  • Brain / growth & development
  • Brain / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / metabolism*
  • D-Aspartic Acid / metabolism*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism
  • Hippocampus / drug effects
  • Hippocampus / growth & development
  • Hippocampus / metabolism*
  • Hydrolysis
  • In Vitro Techniques
  • Phosphatidylinositol Phosphates / metabolism*
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism*

Substances

  • Excitatory Amino Acid Antagonists
  • Phosphatidylinositol Phosphates
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Glutamic Acid
  • D-Aspartic Acid
  • 6-methyl-2-(phenylethynyl)pyridine