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Flunarizine and r-56865 suppress veratridine-induced increase in oxygen-consumption and uptake of ca-45(2+) in rat cortical synaptosomes

WERMELSKIRCHEN, D., GLEITZ, J., URENJAK, J., WILFFERT, B., TEGTMEIER, F. & Peters, T., Mar-1992, In : Neuropharmacology. 31, 3, p. 235-241 7 p.

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  • D WERMELSKIRCHEN
  • J GLEITZ
  • J URENJAK
  • B WILFFERT
  • F TEGTMEIER
  • Thies Peters

The effect of the anti-ischemic compounds flunarizine and R 56865 on the veratridine-induced uptake of Ca2+ and Na+ was observed in cortical synaptosomes in the rat. The veratridine-induced uptake of Na+ and Ca2+ was determined by means of a measurement of synaptosomal oxygen consumption and a method for the uptake of Ca-45(2+), respectively. Veratridine (10(-5) M) was found to induce a 3-fold increase in synaptosomal oxygen consumption (uptake of Na+) and uptake of Ca-45(2+), both of which were inhibited by tetrodotoxin (10(-5) M). Nitrendipine (10(-5) M) and omega-conotoxin (5 x 10(-7) M) were ineffective on the veratridine-induced response. Nimodipine (10(-5) M) suppressed the veratridine-induced uptake of Ca-45(2+) but also diminished the unstimulated uptake of Ca-45(2+). The veratridine-induced uptake of Na+ was not influenced by nimodipine. Flunarizine (3 x 10(-6)-10(-5) M), as well as R 56865 (10(-6)-10(-5) M), attenuated the veratridine-induced uptake of both Na+ and Ca-45(2+). In conclusion, the veratridine-induced uptake of Na+ and Ca-45(2+) was shown to be closely correlated to the activity of Na+ channels but not to voltage-operated Ca2+ channels. Secondly, flunarizine and R 56865 seemed to evoke their effects by interfering with the permeability of Na+ channels. Since veratridine-induced uptake of Na+ and Ca2+ shares some similarities with ischaemia-induced uptake of Na+ and Ca2+, it is proposed, that flunarizine and R 56865 exert their anti-ischaemic effects by reducing ischaemia-induced Na+ and Ca2+ load, probably by inhibiting a TTX-sensitive Na+ channel.

Original languageEnglish
Pages (from-to)235-241
Number of pages7
JournalNeuropharmacology
Volume31
Issue number3
Publication statusPublished - Mar-1992

    Keywords

  • VERATRIDINE, OXYGEN CONSUMPTION, CA-45(2+) UPTAKE, NA+ CHANNEL, CALCIUM CHANNELS, SODIUM INFLUX, NA CHANNELS, BRAIN, ENTRY, TETRODOTOXIN, BINDING, DAMAGE, ANTAGONIST, PRINCIPLE

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