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34682 
Journal Article 
Influence of oxygenated fuel additives and their metabolites on the binding of a convulsant ligand of the "gamma"-aminobutyric acid(A) (GABA(A)) receptor in rat brain membrane preparations 
Martin, JV; Bilgin, NM; Iba, MM 
2002 
1 
Toxicology Letters
ISSN: 0378-4274
EISSN: 1879-3169 
Netherlands 
129 
3 
219-226 
English 
11888705 
WOS:000174882200005 
As a foundation for evaluating potential mechanisms of the neurological effects (e.g. headache, nausea, dizziness) of some octane boosters, we studied the -aminobutyric acidA (GABAA) receptor in a series of binding assays in membranes from rat brain. The GABAA receptor was probed using the radioligand [3H]t-butylbicycloorthobenzoate ([3H]TBOB) which binds to the convulsant recognition site of the receptor. The results demonstrated that the short-chain t-ethers and their t-alcohol metabolites inhibit binding at the convulsant site of the GABAA receptor. The potency of the inhibition tended to correlate with carbon chain length. For agents having an equal number of carbon atoms, potency of inhibition of [3H]TBOB binding was greater in magnitude for the alcohols than for the ethers. The descending rank order of potency for the ethers and alcohols were as follows, t-amyl alcohol (TAA); t-amyl-methyl ether (TAME); ethyl-t-butyl ether (ETBE)>t-butyl alcohol (TBA)>methyl-t-butyl ether (MTBE)>ethanol. In additional saturation binding assays, MTBE reduced apparent density of convulsant binding (Bmax). 
Air Pollutants/metabolism/toxicity; Animals; Bicyclo Compounds, Heterocyclic/metabolism; Binding Sites; Brain/drug effects/metabolism; Dose-Response Relationship, Drug; Ethyl Ethers/pharmacology; Gasoline; Intracellular Membranes/drug effects/metabolism; Male; Methyl Ethers/pharmacology; Pentanols/pharmacology; Rats; Rats, Sprague-Dawley; Receptors, GABA-A/metabolism; Structure-Activity Relationship; tert-Butyl Alcohol/pharmacology; 0; 1634-04-4; 637-92-3; 75-65-0; 75-85-4; 98774-24-4; 994-05-8