Olfactory studies using ethyl bromoacetate and other chemically active odorants

Abstract. Eleven chemically active odorants were tested to determine their effectiveness and specifici-ty in inhibiting electroolfactogram (EOG) responses in the frog olfactory mucosa. These inhibitory agents probably act by several different mechanisms, but they all produced a comparable degree of in-hibition when approximately the same amount of inhibitor had been applied. One agent, ethyl bromoacetate, produced a specific pattern of inhibition in which responses to all odorants tested were inhibited except responses to certain amines. A related agent, ethyl chloroacetate, produced a similar, but less well-defined specific effect. Non-specific inhibitory effects were produced by seven of the agents tested. Two agents produced no inhibition, presumably because their low vapor pressure prevented the application of sufficient reagent in the vapor phase. The majority of the effective in-hibitors are alkylating agents or substrates for nucleophilic addition which react with sulfhydryl or amino groups of proteins. By contrast, the inhibitory effect of diethylamine is probably the result of its basicity. The basicity would enable neutralization reactions with acidic groups of proteins or other substances in the microenvironment of the receptors. Several lines of evidence lead to the conclusion that the inhibitory action of the chemically active odorants is principally the result of disruption of molecular olfactory receptors in the membranes of olfactory neurons, and that sulfhydryl, amino, and carboxyl groups are of importance to the function of olfactory receptors, ion channels, or recep-tor/ionophore macromolecules