Nicotine as an odorant : a biochemical and electrophysiological study of receptors for nicotine in the olfactory epithelium of the rat
The results suggest that nicotine vapour stimulates an in vitro olfactory preparation in three strains of rat and two strains of mouse, in a manner similar to known odorants. Preliminary experiments also suggest that nicotine is an odorant for human subjects. In the rat, the electro-olfactogram (EOG) produced by nicotine is attenuated by superfusion of the olfactory mucosa with the lectin concanavalin A. This reduction is prevented by a-methyl-D-mannoside, suggesting. that there is a glyco-moiety associated with at least one olfactory receptor responding to nicotine. A concanavalin A induced change in EOG response with varying odorant concentration for several odorants, including nicotine, can be explained by a single concanavalin A sensitive olfactory receptor with a dissociation constant for odorant binding in the order of 100 nM. The results also show that hydrophilic odorants are poor stimulants for the olfactory epithelium, supporting the hypothesis that the interaction of an odorant with the olfactory receptors involves hydrophobic effects. Spatial variation in response to four odorants, including nicotine, by the rat olfactory epithelium can be explained by a mosaic of olfactory receptors of various types in the olfactory epithelium. This observation is consistent with current hypotheses of odour quality determination by the olfactory mucosa. Nicotine binding sites in olfactory and respiratory epithelia. Binding studies show that there are sites for 3H(-) nicotine in both olfactory and respiratory preparations, though these sites may not be the same in each tissue. The binding parameters for olfactory epithelium are Ko=695 nM and Bmax=8.24 pmol/mg protein (mean of two experiments at optimal binding conditions). The olfactory epithelium binding sites differ from binding sites for nicotine described elsewhere for brain (e.g. Ko values from 0.2-60 nM, Bmax values from 1-100 fmol/mg protein) and for liver (Ko=0.2 nM, Bmax=5 fmol/mg protein). Some of the 3H(-) nicotine binding may be to an olfactory receptor though more conclusive evidence is required to substantiate this.