In recent years interest has been concentrated on olfactory effects in insects especially after the extensive studies of Butenandt and Hecker and of Jacobson
Π. MOLECULAR APPROACH TO OLFACTION 47 on the isolation, structure, and function of sex attractants. Excellent reviews of the literature on this subject have been published by Butenandt and Hecker (18a), Crescitelli and Geismann (22a), and Hecker (46a).
The work was based upon observations made at an earlier date, according to which female butterflies are able to attract males even at distances of several miles. It was found that this attraction is caused by the female secre
tion of organic materials of specific structure which are observed by the male by means of an olfactive mechanism. The latter has been demonstrated particularly by the electrophysiological studies of Schneider (82a-c) on the antennae of the silkworm moth and of several saturniid species.
In some cases the structure of the attractants has been elucidated. The attracting substance of the silkworm moth (Bombyx mori), which was named
"Bombykol" by its discoverer Butenandt, was found to have the structure ΙΟ-trans- 12-c*Vhexadecadienol-1 (XL VIII).
Η Η H3COCO Η Η
C H3C H2C H2 C = C CH3(CH2)5CHCH2 (CH2)5CH2OH Η \ ( C H2)8C H2O H
(XLVIII) ( X L I X )
The action on the receptors requires a high specificity in structure; the threshold values for the three stereomers of XLVIII are reported to be 108-1014 times higher than that of XLVIII.
The attracting substance of the gypsy moth (Lymantria dispar) was found by Jacobson to be ( + ) — 10-acetoxy-7-ciVhexadecenol-l (XLIX).
Both substances are extremely active and highly specific, and their avail
ability offers unique possibilities for the study of cellular physiology and the pharmacology of the sense organs.
Also, the increased knowledge about sex attractants in insects is of con
siderable practical importance because of the possibilities of their application in insect control.
As mentioned in the introduction, the molecular aspects of taste are not discussed here. As a matter of fact there are points of similarity between ol
faction and gustation. Some of the molecular aspects of taste are discussed in Volume I of "Molecular Pharmacology," Section II.A.4.2 (7a). For further information on this topic the reader is referred to a recent review by Beidler (13a), Tucker (91a), and Zotterman (100a).
X. CONCLUSION S
In the introduction to this chapter some problems of fundamental importance to olfaction were formulated. Now, after having reviewed the most important data in the literature, we may strike a balance in order to find out how much we know, how much we may safely assume, and where further work is most needed.
One question at least can be answered with encouraging certainty; the inter
action between stimulant and olfactory membrane takes place by material contact.
The structure of the receptor organ is known in great detail up to anatomical and histological levels. However, beyond these levels, very little information has been obtained. Some insight into the fine structure and the chemical compo
sition of the olfactory membrane is especially needed and would be very helpful in increasing our knowledge of the mechanism of the interaction. It is surprising that even the relatively easy problem of the composition and the structure of the olfactory pigments still remains unsolved.
Some insight into the geography of the olfactory epithelium has been obtained. We know that olfaction is restricted to the colored region, and that the tendency to interact with certain stimulant molecules is not evenly distri
buted. The experimental data indicate strongly that each receptor unit has a part or complete specificity in interaction with molecules of one structure, or group of related structures, and that the nature of the stimulus is at least partly determined by the geography of its formation on the olfactory epithelium. It seems probable that the temporal differentiation, proposed by Adrian and interpreted by Ottoson as being brought about by the different water and lipid solubilities of the stimulant, also plays an important part.
At the moment it seems safe to assume that the fine structure of the inter
action, which is the direct source of the quality of the odor impression, is delineated by the structure and the concentration of the stimulant, by the geographical distribution of its interaction with the receptors and by the temporal differentiation of this interaction.
Further, we may assume that interaction is preceded or accompanied by adsorption of the stimulant molecule in a preferred orientation determined by the distribution of functional groups, or, when the latter are absent or inade
quate, in a more or less random orientation and that in this selected orientation, the profile of each molecule determines its part in the interaction. This implies clearly that the function of the stimulant molecule in the mechanism of ol
faction is a physical one, i.e., that the odorant molecule as well as the constituent molecules of the receptor, involved in the interaction, do not undergo any permanent chemical change.
A mechanism of interaction involving permanent structural changes of the interaction partners may definitely be rejected on account of the nonspecificity of the functional group and of the huge variety of structural classes comprising odorant compounds.
Finally, we have collected many scraps of information on various aspects of olfaction which, in due time may fit together to complete the picture but which are, at this moment, too unrelated to be very helpful. On the crucial problem of olfaction, the mechanism of the interaction, we know practically nothing, although some interesting suggestions, such as the analogy between hemolysis
II. MOLECULAR APPROACH TO OLFACTION 49 and olfaction observed by Da vies and Taylor, await further investigation. In spite of our limited knowledge and the many unsuccessful and often inexpert approaches towards a solution in the first decennia of this century, the chances of finding the ultimate solution of the problem of olfaction seem rather favor
able. The main reason for this is, that several techniques for further research are now available. The best and most detailed results can, of course, be expected from further application of electrophysiological methods. Systematic attempts to map the distribution of sensitivity to different odorants over the olfactory region seem to be necessary. Such work may be assisted by the method of selec
tive adaptation (Ottoson; Le Magnen). Careful statistical work on the behavior of animals of the type described by Dethier and by Le Magnen, continued studies on the relation between olfaction and physiological conditions (Le Magnen), and finally chemical analysis of the constituents of the olfactory region, especially on the structure of the olfactory pigments, can be expected to yield additional information.
Since a detailed knowledge of the mechanism of olfaction would undoubtedly entail many suggestions on analogous aspects of other fields of pharmacology, over which it has the considerable advantage of the unusually clear position of the receptor organ, this field of research deserves a more concentrated interest by serious scientists than it has obtained in the past.
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