Flupirtine ameliorates ischaemic-like death of rat retinal ganglion cells by preventing calcium influx

Flupirtine ameliorates ischaemic-like death of rat retinal ganglion cells by preventing calcium... The effect of flupirtine on the loss of retinal ganglion cells following transient elevation of intraocular pressure (experimental ischaemia) or NMDA-induced excitotoxicity was studied. Ischaemia (60 min) or intravitreal injection of NMDA (20 nmol) caused a decrease in Thy-1 mRNA and Thy-1 immunoreactivity which are associated with ganglion cells. Administration of flupirtine counteracted these changes. Moreover, flupirtine dose-dependently inhibited NMDA-induced 45 Ca 2+ influx into cultured cortical neurones and retinal pieces in vitro with maximal inhibition being observed at 200 μM. A similar concentration of flupirtine failed to inhibit kainate-stimulated calcium influx into cultured cortical neurones. In addition, flupirtine had no significant effect on ( 3 H )nitrendipine or ( 3 H )diltiazem binding to cortical membranes. The present studies are consistent with previous findings which suggested flupirtine to act as a NMDA antagonist by a mechanism that still remains to be clarified. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Flupirtine ameliorates ischaemic-like death of rat retinal ganglion cells by preventing calcium influx

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Publisher
Elsevier
Copyright
Copyright © 2000 Elsevier Science B.V.
ISSN
0006-8993
D.O.I.
10.1016/S0006-8993(99)02278-7
Publisher site
See Article on Publisher Site

Abstract

The effect of flupirtine on the loss of retinal ganglion cells following transient elevation of intraocular pressure (experimental ischaemia) or NMDA-induced excitotoxicity was studied. Ischaemia (60 min) or intravitreal injection of NMDA (20 nmol) caused a decrease in Thy-1 mRNA and Thy-1 immunoreactivity which are associated with ganglion cells. Administration of flupirtine counteracted these changes. Moreover, flupirtine dose-dependently inhibited NMDA-induced 45 Ca 2+ influx into cultured cortical neurones and retinal pieces in vitro with maximal inhibition being observed at 200 μM. A similar concentration of flupirtine failed to inhibit kainate-stimulated calcium influx into cultured cortical neurones. In addition, flupirtine had no significant effect on ( 3 H )nitrendipine or ( 3 H )diltiazem binding to cortical membranes. The present studies are consistent with previous findings which suggested flupirtine to act as a NMDA antagonist by a mechanism that still remains to be clarified.

Journal

Brain ResearchElsevier

Published: Feb 21, 2000

References

  • Expression of NMDA and high-affinity kainate receptor subunit mRNAs in the adult rat retina
    Brandstätter, J.H.; Hartveit, E.; Sassoe Pognetto, M.; Wässle, H.
  • Melatonin protects primary cultures of rat cortical neurones from NMDA excitotoxicity and hypoxia/reoxygenation
    Cazevieille, C.; Safa, R.; Osborne, N.N.
  • Protection of rabbit retina from ischaemic injury by flupirtine
    Osborne, N.N.; Schwarz, M.; Pergande, G.

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