Actions of picrotoxinin analogues on an expressed, homo-oligomeric 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 expressed in Xenopus oocytes. In agreement with previously reported studies on native insect G...

Full description

Saved in:
Bibliographic Details
Published in:Neuroscience letters 1995-04, Vol.189 (1), p.1-4
Main Authors: SHIRAI, Y, HOSIE, A. M, BUCKINGHAM, S. D, HOLYOKE, C. W, BAYLIS, H. A, SATTELLE, D. B
Format: Article
Language:English
Subjects:
Acetylation
Animals
Biochemistry. Physiology. Immunology
Biological and medical sciences
Drosophila melanogaster
Drosophila melanogaster - metabolism
Female
Fluorine - metabolism
Fundamental and applied biological sciences. Psychology
Insecta
Invertebrates
Oocytes - metabolism
Physiology. Development
Picrotoxin - analogs & derivatives
Picrotoxin - chemistry
Picrotoxin - metabolism
Picrotoxin - pharmacology
Receptors, GABA - chemistry
Receptors, GABA - drug effects
Structure-Activity Relationship
Water - metabolism
Xenopus
Xenopus laevis
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0304-3940
1872-7972