Group I mGluR ligands fail to affect 6-hydroxydopamine- induced death and glutamate release of PC12 cells

Acta Pharmacol Sin. 2003 Jul;24(7):641-5.

Abstract

Aim: To study the effect of group I metabotropic glutamate receptor (mGluR) ligands on 6-hydroxydopamine (6-OHDA)-induced death and glutamate release of PC12 cells.

Methods: PC12 cells were exposed to 100 micromol/L of group I mGluR agonist (RS)-3,5-dihydroxy-phenylglycine (DHPG) or antagonist DL-2-amino-3-phosphonopropionic acid (DL-AP3) 1 h before addition of 6-OHDA 100 micromol/L. After incubation for 24 h, morphological alterations were observed with microscope, DNA fragmentation was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method, cytotoxicity was measured by MTT assay, and glutamate release was assayed by high performance liquid chromatography.

Results: 6-OHDA decreased cell viability (P<0.01) and induced concentration- and time-dependent glutamate release from PC12 cells. Group I mGluR ligands did not affect 6-OHDA-induced death of PC12 cells and had no influence on glutamate levels.

Conclusion: Group I mGluR ligands cannot protect PC12 cells from 6-OHDA-induced death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Agents / pharmacology
  • Alanine / analogs & derivatives*
  • Alanine / pharmacology
  • Animals
  • Apoptosis*
  • Cell Survival / drug effects
  • DNA Fragmentation
  • Drug Interactions
  • Glutamic Acid / metabolism*
  • Ligands
  • Methoxyhydroxyphenylglycol / analogs & derivatives*
  • Methoxyhydroxyphenylglycol / pharmacology*
  • Oxidopamine / pharmacology*
  • PC12 Cells
  • Rats
  • Receptors, Metabotropic Glutamate / agonists*
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors

Substances

  • Adrenergic Agents
  • Ligands
  • Receptors, Metabotropic Glutamate
  • 2-amino-3-phosphonopropionic acid
  • Glutamic Acid
  • Methoxyhydroxyphenylglycol
  • Oxidopamine
  • Alanine
  • 3,4-dihydroxyphenylglycol