Different effects on [3H]noradrenaline uptake of the Aconitum alkaloids aconitine, 3-acetylaconitine, lappaconitine, and N-desacetyllappaconitine in rat hippocampus.
The effect of the Aconitum alkaloids aconitine, 3-acetylaconitine, lappaconitine, and N-desacetyllappaconitine to inhibit [3H]noradrenaline uptake was investigated in rat hippocampal synaptosomes. Aconitine and 3-acetylaconitine, which are known to activate sodium channels, had comparable inhibitory potencies and yielded Ki (inhibitor constant) values of 230 +/- 66 nM and 316 +/- 96 nM, respectively. In contrast, lappaconitine and N-desacetyllappaconitine failed to inhibit [3H]noradrenaline uptake. When either lappaconitine or N-desacetyllappaconitine was applied in combination with aconitine, [3H]noradrenaline uptake was not affected. The sodium channel blocker tetrodotoxin enhanced [3H]noradrenaline uptake, whereas uptake was completely blocked in sodium-free incubation medium. The inhibitory action of aconitine and 3-acetylaconitine on [3H]noradrenaline uptake was blocked by addition of tetrodotoxin. Patch clamp studies performed on cultured rat hippocampal neurons revealed an inhibitory action of lappaconitine and N-desacetyllappaconitine on whole cell sodium currents. It is concluded that the blockade of [3H]noradrenaline uptake evoked by aconitine and 3-acetylaconitine is mediated indirectly by an increased sodium concentration in the synaptosomes.
Seitz
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U
Department of Pharmacy and Pharmacology of Natural Compounds, University of Ulm, Germany.
Ameri
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D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010946:Plants, Medicinal; D017966:Pyramidal Cells / Q000187:drug effects; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects; D014316:Tritium
D014316:Tritium; C055260:N-deacetyllappaconitine; C031321:3-acetylaconitine; D009638:Norepinephrine; D000157:Aconitine; C022150:lappaconitine