The role of perceptual and structural similarity in cross-adaptation.

Cross-adaptation, the decrease in sensitivity to one odorant following exposure to a different odorant, is affected by odorant similarity, both perceptual and structural, but the precise relationship is obscure. The present series of studies was designed to explore various aspects of perceptual and structural similarity as they relate to cross-adaptation. In Experiment 1, cross-adaptation was assessed between androstenone and five odorants that share a common urinous note with androstenone, but retain unique perceptual characteristics; only the compound judged most perceptually similar to androstenone cross-adapted it. In Experiment 2, odorants both perceptually and structurally similar (androstenone and androstanone) displayed significant, mutual cross-adaptation. Furthermore, magnitude estimates for androstanone were significantly reduced following exposure to 3-methylidene-5 alpha-androstane (3M5A), a structurally similar, perceptually odorless compound. This finding appears to be the first demonstration that an odorless compound can affect, via cross-adaptation, the perception of an odorous compound. Finally, in Experiment 3, significant, asymmetric cross-adaptation was observed between compounds that are perceptually and structurally dissimilar (4-cyclohexylcyclohexanone [4-CHCH] and androstenone). These findings indicate that the role of similarity in cross-adaptation is difficult to quantify and emphasize the numerous odorant characteristics that can affect cross-adaptation.

Capsaicin and its analogs induce ion channels in planar lipid bilayers.

The irritating, pungent compound, capsaicin (10-20 microM), induces the formation of non-selective ion channels with a wide variety of conductances in protein-free lipid bilayers form from a mixture of zwitterionic phospholipids. The channel-forming activity of capsaicin and four of its analogs followed the sequence: resiniferatoxin > capsaicin = pelargonic acid vanillylamide > methylcapsaicin >> veratrylamine. The ability to form channels correlated with the biological activity of these compounds observed in other studies that measured 45Ca uptake into rat dorsal root ganglion cells. The correlation obtained suggests that an interaction with the lipid bilayer may be an important component of the biological activity of capsaicin.

Cross-adaptation of sweaty-smelling 3-methyl-2-hexenoic acid by a structurally-similar, pleasant-smelling odorant.

Cross-adaptation has been interpreted as a measure of the degree to which odors share common sensory channels. How structural similarity, in the absence of perceptual similarity, influences cross-adaptation is unknown. The present study assessed cross-adaptation by structurally similar, but perceptually different, odorants. Magnitude estimates for a 10:1 mixture of (E)- and (Z)-3-methyl-2-hexenoic acid (3M2H), a principal component of human underarm odor, decreased following adaptation to a mixture of (E)- and (Z)-ethyl esters of 3M2H (EE3M2H), which possess a pleasant, fruity odor. Cross-adaptation was asymmetric; adaptation to 3M2H did not significantly affect the perceived intensity of EE3M2H. By contrast, there was no significant cross-adaptation between 3M2H and the fruity-smelling ethyl esters of its homologues, 3-methyl-2-octenoic acid (EE3M20) and 3-methyl-2-pentenoic acid (EE3M2P). Similarity ratings revealed no differences among the three ethyl esters in their perceptual similarity to 3M2H (i.e. all were rated equally dissimilar to 3M2H). Molecular modeling studies revealed no difference in the charge distribution of these molecules. Rather, differences in the shape and size of the hydrophobic part of the molecule may determine the extent of cross-adaptation. These results demonstrate that structurally-similar, yet perceptually-distinct, odorants may cross-adapt and suggest that the extent of cross-adaptation may be affected by the degree of structural, as well as perceptual, similarity.

The properties of ion channels formed by the coumarin antibiotic, novobiocin, in lipid bilayers.

The coumarin antibiotic novobiocin forms ion channels of varying conductances in lipid bilayers. The conductances (about 20, 22, 14, 7 and 2 pS for 100 mM NH4Cl, CsCl, KCl, NaCl and LiCl, respectively) and selectivities (cation transference numbers in the range of 0.97-0.98) of one type of novobiocin-induced channel are similar to those found for channels formed by gramicidin A, an antibiotic of very different structure. The conductance of novobiocin channels of this type was independent of the species of the membrane lipid. This observation suggests that novobiocin molecules directly form these channels, and that channels are not formed through defects in lipid structure. The similarity in conductance and ion selectivity between channels induced by novobiocin and those formed by gramicidin A suggests that these structurally different molecules form channels with comparable internal diameter and internal surface charge distribution. Using HPLC purification we argue that the channel-forming activity of novobiocin is related to the activity of the novobiocin molecule itself, and not to a contaminant of the commercially available novobiocin sodium salt preparation.