Flunarizine and R 56865 suppress veratridine-induced increase in oxygen consumption and uptake of45Ca2+in rat cortical synaptosomesWermelskirchen, D., Gleitz, J., Urenjak, J., Wilffert, B., Tegtmeier, F. & Peters, T., 22-Oct-1992, In : Neuropharmacology. 31, 3, p. 235-241 7 p.
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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 of45Ca2+, respectively. Veratridine (10-5M) was found to induce a 3-fold increase in synaptosomal oxygen consumption (uptake of Na+) and uptake of45Ca2+, both of which were inhibited by tetrodotoxin (10-5M). Nitrendipine (10-5M) and ω-conotoxin (5 x 10-7M) were ineffective on the veratridine-induced response. Nimodipine (10-5M) suppressed the veratridine-induced uptake of45Ca2+but also diminished the unstimulated uptake of45Ca2+. The veratridine-induced uptake of Na+was not influenced by nimodipine. Flunarizine (3 x 10-6-10-5M), as well as R 56865 (10-6-10-5M), attenuated the veratridine-induced uptake of both Na+and45Ca2+. In conclusion, the veratridine-induced uptake of be N+and45Ca2+was shown to be closely correlated to the activity of Na+channels but not to voltage-oporated 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.
|Number of pages||7|
|Publication status||Published - 22-Oct-1992|
- 45Ca2+uptake, Na+channel, oxygen consumption, veratridine, antiischemic agent, cardiovascular agent, flunarizine, n [1 [4 (4 fluorophenoxy)butyl] 4 piperidinyl] n methyl 2 benzothiazolamine, nimodipine, nitrendipine, omega conotoxin, radioisotope, tetrodotoxin, unclassified drug, animal tissue, article, brain cortex, brain synaptosome, calcium transport, controlled study, nonhuman, priority journal, rat, sodium transport