Comparison of lindane, bicyclophosphate and picrotoxin binding to the putative chloride channel sites in rat brain and Torpedo electric organ

Neurotoxicol Teratol. 1990 Jan-Feb;12(1):57-63. doi: 10.1016/0892-0362(90)90113-q.

Abstract

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.

Publication types

  • Comparative Study

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*
  • Hexachlorocyclohexane / metabolism*
  • Membrane Proteins / metabolism*
  • Picrotoxin / metabolism*
  • Rats
  • Rats, Inbred F344
  • Receptors, GABA-A / metabolism
  • Species Specificity
  • Torpedo

Substances

  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Bridged-Ring Compounds
  • Chloride Channels
  • Chlorides
  • Membrane Proteins
  • Receptors, GABA-A
  • Picrotoxin
  • Hexachlorocyclohexane
  • tert-butylbicyclophosphorothionate
  • Bicuculline