Shirai Y, Hosie A M, Buckingham S D, Holyoke C W, Baylis H A, Sattelle D B
Graduate School of Science and Technology, Kobe University, Hyogo Japan.
Neurosci Lett. 1995 Apr 7;189(1):1-4. doi: 10.1016/0304-3940(95)11432-v.
The actions of picrotoxinin and four of its analogues were tested on a Drosophila melanogaster homo-oligomeric GABA (gamma-aminobutyric acid) receptor formed when RDL (resistance to dieldrin) subunits were expressed in Xenopus oocytes. In agreement with previously reported studies on native insect GABA receptors and native expressed vertebrate GABA receptors, acetylation of the bridgehead hydroxyl group (picrotoxinin acetate) greatly reduced the activity of the molecule, but surprisingly, substitution with flourine at the same position also reduced the activity. Conversion of the terminal isopropenyl group to an acetyl (alpha-picrotoxinone) or hydration of the double bond (picrotin) also reduced activity, in agreement with findings for native insect and mammalian receptors. The present results suggest that interactions of convulsants with homo-oligomeric and multimeric GABA receptors are qualitatively similar. Thus, the RDL homo-oligomer exhibits a pharmacological profile for picrotoxinin analogues resembling that of native GABA receptors.
在非洲爪蟾卵母细胞中表达抗狄氏剂（RDL）亚基时形成的果蝇同源寡聚γ-氨基丁酸（GABA）受体上，测试了印防己毒素及其四种类似物的作用。与先前关于天然昆虫GABA受体和天然表达的脊椎动物GABA受体的研究一致，桥头羟基的乙酰化（印防己毒素乙酸酯）大大降低了分子的活性，但令人惊讶的是，在同一位置用氟取代也降低了活性。末端异丙烯基转化为乙酰基（α-印防己毒素酮）或双键水合（印防己苦毒素）也降低了活性，这与天然昆虫和哺乳动物受体的研究结果一致。目前的结果表明，惊厥剂与同源寡聚体和多聚体GABA受体的相互作用在性质上是相似的。因此，RDL同源寡聚体对印防己毒素类似物表现出类似于天然GABA受体的药理学特征。
