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.
As a foundation for evaluating potential mechanisms of the neurological effects (e.g. headache, nausea, dizziness) of some octane boosters, we studied the gamma-aminobutyric acid(A) (GABA(A)) receptor in a series of binding assays in membranes from rat brain. The GABA(A) 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 GABA(A) 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 (B(max)).
Martin
Joseph V
JV
Department of Biology, Rutgers University, 315 Penn Street, Camden, NJ 08055, USA. jomartin@cadem.rutgers.edu
Bilgin
Nesli M
NM
Iba
M Michael
MM
D000393:Air Pollutants / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005019:Ethyl Ethers / Q000494:pharmacology; D005742:Gasoline; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D000439:Pentanols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship; D020002:tert-Butyl Alcohol / Q000494:pharmacology
D000393:Air Pollutants; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005019:Ethyl Ethers; D005742:Gasoline; D008738:Methyl Ethers; D000439:Pentanols; D011963:Receptors, GABA-A; C043243:methyl tert-butyl ether; C098546:ethyl tert-butyl ether; C032765:tert-amyl alcohol; C096680:tertiary-amyl methyl ether; C046308:tert-butylbicyclo-2-benzoate; D020002:tert-Butyl Alcohol