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Selective NR2B NMDA receptor antagonists are protective against staurosporine-induced apoptosis

Anthony J Williams1, Jitendra R Dave, X May Lu

  • 1Walter Reed Army Institute of Research, Silver Spring, MD, USA. SPCAnthony.Williams@na.amedd.army.mil

European Journal of Pharmacology
|September 27, 2002
PubMed

Insights

Selective NR2B receptor antagonists, conantokin-G and ifenprodil, protected primary rat neurons from staurosporine-induced apoptosis. This suggests a novel anti-apoptotic mechanism involving the NR2B subunit.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Apoptosis, or programmed cell death, is a critical process in neuronal development and disease.
  • The N-methyl-D-aspartate (NMDA) receptor, particularly its NR2B subunit, plays a role in neuronal survival and excitotoxicity.

Purpose of the Study:

  • To investigate the role of the NR2B subunit of the NMDA receptor in neuronal apoptosis.
  • To evaluate the neuroprotective effects of selective NR2B antagonists against staurosporine-induced cell death.

Main Methods:

  • Primary rat forebrain cultures were treated with staurosporine to induce apoptosis.
  • Cellular survival rates were measured after treatment with various NMDA receptor antagonists, including selective NR2B antagonists (conantokin-G, ifenprodil) and a nonselective antagonist (dizocilpine).

Main Results:

  • Staurosporine induced apoptosis, resulting in a 20% cellular survival rate.
  • Conantokin-G (0.1-1 microM) significantly increased survival to 78%.
  • Ifenprodil (0.01-10 microM) provided 34-64% cellular survival, while dizocilpine showed no protective effect.

Conclusions:

  • The NR2B subunit of the NMDA receptor is implicated in a novel anti-apoptotic mechanism.
  • Selective NR2B antagonism demonstrates significant neuroprotective potential against apoptosis.

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