Influence of oxygenated fuel additives and their metabolites on the binding of a convulsant ligand of the γ-aminobutyric acid A (GABA A) receptor in rat brain membrane preparations

Abstract

As a foundation for evaluating potential mechanisms of the neurological effects (e.g. headache, nausea, dizziness) of some octane boosters, we studied the γ-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).