Various Ca2+ entry blockers prevent glutamate-induced neurotoxicity

https://doi.org/10.1016/0014-2999(91)90166-NGet rights and content

Abstract

In the present study we investigated the effect of different Ca2+ entry blockers on the onset of neuronal damage induced by glutamate, kainate or α-amino-3-hydroxy-5-methyl-5-isoxazolo propionate (AMPA) in primary culture of rat cerebellar granule cells. We found that the dihydropyridine derivative, nifedipine used at 100 nM concentration, significantly counteracted the neuronal death induced by 15 min application of 50 μM glutamate. This effect was dependent on the presence of nifedipine before the exposure of granule cells to glutamate and was dose-related (IC50 = 10 nM). The nifedipine response was reproduced by isradipine and by verapamil with IC50 values of 9 and 100 nM, respectively. The activation of voltage sensitive Ca2+ channels elicited by 100 nM Bay K 8644, greatly enhanced glutamate-mediated neurotoxicity. Moreover, 100 nM isradipine was significantly active in blocking the neuronal death produced by 24 h exposure of cerebellar granule cells to 10 μM AMPA or 60 μM kainate. These results reveal a ‘preventive’ role of the Ca2+ entry blockers on the development of the neurodegeneration induced by overstimulation of various glutamate receptor subtypes.

References (29)

  • B. Engelsen

    Neurotransmitter glutamate: its clinical importance

    Acta Neurol. Scand.

    (1986)
  • A. Fujisawa et al.

    The effect of the calcium antagonist nimodipina on the gerbil model of experimental cerebral ischemia

    Stroke

    (1986)
  • R.J. Gould et al.

    [3H] Nitrendipine-labeled calcium channels discriminate inorganic calcium agonists and antagonists

  • J.T. Greenamyre

    The role of glutamate in neurotransmission and in neurologic disease

    Arch. Neurol.

    (1986)
  • Cited by (0)

    View full text