Article date: 1990/1/1
PubMed ID: 1690344
Journal name: Neurotoxicology and teratology (ISSN: 0892-0362)
The relative potencies of lindane, picrotoxin and several bicyclophosphate derivatives were compared in their ability to compete with 35S-t-butylbicyclophosphorothionate (35S-TBPS) binding sites in membranes derived from Torpedo electric organ and rat brain. Lindane proved to be ten times more potent in competing with 35S-TBPS binding in electric organ than rat brain, while the bicyclophosphate analogs displayed up to three orders of magnitude greater affinity for rat brain over electric organ. GABA inhibited 35S-TBPS binding in rat brain with moderate potency (IC50 = 30 microM), while unlabelled TBPS inhibited the binding of 3H-muscimol to the GABA receptor with an IC50 greater than 100 microM. The GABA receptor antagonist bicuculline increased 35S-TBPS binding in rat brain both in the presence and absence of 30 microM GABA. The results of the study are discussed in the context of a pharmacological discrimination between voltage-sensitive and receptor-gated Cl- channels in nervous tissue, with lindane and the i-propylbicyclophosphate derivative being the most selective compounds for discriminating between them.
Author List: Thompson R G, Menking D E, Valdes J J
Publication Types: Comparative Study; Journal Article
Substances mentioned in the article: Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Bridged-Ring Compounds; Chloride Channels; Chlorides; Membrane Proteins; Receptors, GABA-A; Picrotoxin; Lindane; tert-butylbicyclophosphorothionate; Bicuculline;
Mesh terms: Animals; Bicuculline/pharmacology; Binding Sites; Brain/metabolism; Bridged Bicyclo Compounds/metabolism; Bridged Bicyclo Compounds, Heterocyclic; Bridged-Ring Compounds/metabolism; Chloride Channels; Chlorides/metabolism; Electric Organ/metabolism; Lindane/metabolism; Membrane Proteins/metabolism; Picrotoxin/metabolism; Rats; Rats, Inbred F344; Receptors, GABA-A/metabolism; Species Specificity; Torpedo;