Activation of metabotropic glutamate receptors prevents neuronal apoptosis in culture

J Neurochem. 1995 Jan;64(1):101-8. doi: 10.1046/j.1471-4159.1995.64010101.x.


Cultured granule cells grown in serum-containing medium with a "low K+" concentration (10 mM) underwent apoptosis after maturation for 5 days in vitro (5 DIV), a time that coincides with the developmental decline in the activity of metabotropic glutamate receptors (mGluRs) coupled to polyphosphoinositide hydrolysis. The mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) prevented the development of low K(+)-induced apoptosis and the presence of the drug was critical at 6 and 7 DIV, i.e., after the drop of mGluR activity. The neuroprotective action of 1S,3R-ACPD was prevented by the mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) and was mimicked by N-methyl-D-aspartate or carbamylcholine but not by agonists of the mGluR subtypes negatively linked to adenylyl cyclase. In cultures treated either with Li(+)-which reduced polyphosphoinositide response to concentrations of glutamate (5 microM) that approximate those physiologically present in the incubation medium--or MCPG, the development of low K(+)-induced apoptosis already occurred at 4 DIV. Thus, the activation of mGluRs coupled to polyphosphoinositide hydrolysis by endogenous glutamate could contribute to protect cultured granule cells against apoptosis during early stages of maturation.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cells, Cultured
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Dose-Response Relationship, Drug
  • Glutamates / pharmacology
  • Microscopy, Fluorescence
  • Neurons / cytology*
  • Neurons / physiology
  • Potassium / pharmacology
  • Rats
  • Receptors, Glutamate / physiology*


  • Glutamates
  • Receptors, Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Potassium