ACTIONS OF PICROTOXININ ANALOGS ON AN EXPRESSED, HOMOOLIGOMERIC GABA RECEPTOR OF DROSOPHILA-MELANOGASTER

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 expr essed in Xenopus oocytes. In agreement with previously reported studie s on native insect GABA receptors and native and expressed vertebrate GABA receptors, acetylation of the bridgehead hydroxyl group (picrotox inin acetate) greatly reduced the activity of the molecule, but surpri singly, substitution with fluorine at the same position also reduced t he 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 ma mmalian receptors. The present results suggest that interactions of co nvulsants with homo-oligomeric and multimeric GABA receptors are quali tatively similar. Thus, the RDL homo-oligomer exhibits a pharmacologic al profile for picrotoxinin analogues resembling that of native GABA r eceptors.