Flunarizine and R 56865 suppress veratridine-induced increase in oxygen consumption and uptake of45Ca2+in rat cortical synaptosomes
| Autor: | Bob Wilffert, J Gleitz, Thies Peters, Detlef Wermelskirchen, Frank Tegtmeier, J. Urenjak |
|---|---|
| Přispěvatelé: | Methods in Medicines evaluation & Outcomes research (M2O), Reproductive Origins of Adult Health and Disease (ROAHD) |
| Jazyk: | angličtina |
| Rok vydání: | 1992 |
| Předmět: |
flunarizine
chemistry.chemical_compound Piperidines Nitrendipine calcium transport veratridine rat Flunarizine tetrodotoxin Cerebral Cortex Voltage-dependent calcium channel Calcium Radioisotopes article sodium transport oxygen consumption unclassified drug Biochemistry priority journal Na+channel Veratridine medicine.drug Sodium omega conotoxin chemistry.chemical_element antiischemic agent In Vitro Techniques Calcium animal tissue brain cortex 45Ca2+uptake Na+channel Cellular and Molecular Neuroscience medicine Animals controlled study Benzothiazoles radioisotope Pharmacology brain synaptosome nonhuman nimodipine Omega-Conotoxins Rats Thiazoles chemistry 45Ca2+uptake cardiovascular agent Cardiovascular agent Biophysics nitrendipine n [1 [4 (4 fluorophenoxy)butyl] 4 piperidinyl] n methyl 2 benzothiazolamine Polarography Synaptosomes |
| Zdroj: | Neuropharmacology, 31(3), 235-241. PERGAMON-ELSEVIER SCIENCE LTD |
| ISSN: | 0028-3908 |
| Popis: | The effect of the anti-ischemic compounds flunarizine and R 56865 on the veratridine-induced uptake of Ca 2+ and Na + was observed in cortical synaptosomes in the rat. The veratridine-induced uptake of Na + and Ca 2+ was determined by means of a measurement of synaptosomal oxygen consumption and a method for the uptake of 45 Ca 2+ , respectively. Veratridine (10 −5 M) was found to induce a 3-fold increase in synaptosomal oxygen consumption (uptake of Na + ) and uptake of 45 Ca 2+ , both of which were inhibited by tetrodotoxin (10 −5 M). Nitrendipine (10 −5 M) and ω-conotoxin (5 × 10 −7 M) were ineffective on the veratridine-induced response. Nimodipine (10 −5 M) suppressed the veratridine-induced uptake of 45 Ca 2+ but also diminished the unstimulated uptake of 45 Ca 2+ . The veratridine-induced uptake of Na + was not influenced by nimodipine. Flunarizine (3 × 10 −6 –10 −5 M), as well as R 56865 (10 −6 –10 −5 M), attenuated the veratridine-induced uptake of both Na + and 45 Ca 2+ . In conclusion, the veratridine-induced uptake of Na + and 45 Ca 2+ was shown to be closely correlated to the activity of Na + channels but not to voltage-operated Ca 2+ 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 Ca 2+ shares some similarities with ischaemia-induced uptake of Na + and Ca 2+ , it is proposed, that flunarizine and R 56865 exert their anti-ischaemic effects by reducing ischaemia-induced Na + and Ca 2+ load, probably by inhibiting a TTX-sensitive Na + channel. |
| Databáze: | OpenAIRE |
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