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

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.