Neuroexcitatory Drug Receptors in Mammals and Invertebrates.
Abstract
The Gamma-aminobutyric acid (GABA) receptor-chloride channel complex and its interaction with convulsant and neurotoxic drugs was studied in mammalian brain and invertebrates by a combination of biochemical and physiological techniques. The GABA receptor complex was assayed in vitro by radioactive ligand binding studies with membrane homogenates from rat brain, insect ganglia, and crayfish muscle. The first binding assay for GABA receptors in the latter two tissues, using (Tritium) muscimol, and the first binding asay for GAGBA receptor-coupled chloride channels, using (Tritium) picrotoxin and (Sulfur 35)t-butyl bicyclophosphorothionate (TBPS) were described. The GABA receptor complex in mammalian brain was shown by binding assays to interact with a variety of convulsant and depressant drugs, including picrotoxin-like cage convulsants (very toxic to mammals), barbiturates, benzodiazepine, amidine steriod convulsants, and several pesticides (avermectins, cyclodiene and polychlorinated hydrocarbon insecticides, and pyrethroids). All of these agents were studied electrophysiologically on crayfish and insect preparations, revealing that picrotoxin and cage convulsants were weak GABA antagonists, cyclodienes and avermections potently modulated GABA responses, and the others (pyrethroids, barbiturates, benzodiazepines, and steriods) were inactive.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 30, 1986
- Accession Number
- ADA175619
Entities
People
- Richard W. Olsen
- Thomas A. Miller
Organizations
- University of California, Los Angeles