Kavain, dihydrokavain, and dihydromethysticin non-competitively inhibit the specific binding of [3H]-batrachotoxinin-A 20-alpha-benzoate to receptor site 2 of voltage-gated Na+ channels.
The mode of action of the kava pyrones, kavain, dihydrokavain and dihydromethysticin on the specific binding of [3H]-batrachotoxinin-A 20-alpha-benzoate to epitope 2 of voltage-dependent Na+ channels was investigated by performing saturation experiments in the presence and absence of these kava pyrones. The tested compounds significantly decreased the apparent total number of binding sites (Bmax) for [3H]-batrachotoxinin-A 20-alpha-benzoate (control: 0.5 pmol/mg protein, kava pyrones: 0.2-0.27 pmol/mg protein) with little change in the equilibrium constants (KD) for [3H]-batrachotoxin-A 20-alpha-benzoate (control: 28.2 nM, kava pyrones: 24-31 nM). The results indicate for the kava pyrones a non-competitive inhibition of the specific [3H]-batrachotoxinin-A 20-alpha-benzoate binding to receptor site 2 of voltage-gated Na+ channels.
J
J
Friese
J
J
Gleitz
D000818:Animals; D001496:Batrachotoxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D015640:Ion Channel Gating; D008297:Male; D011485:Protein Binding; D011753:Pyrones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014316:Tritium
C107882:7,8-dihydromethysticin; D001496:Batrachotoxins; D011753:Pyrones; D015222:Sodium Channels; D014316:Tritium; C113859:dihydrokavain; C031775:batrachotoxinin A 20-alpha-benzoate; C011889:kavain