Olfactory Discrimination Ability of Asian Elephants (Elephas maximus) for Structurally Related Odorants

Rizvanovic, Alisa; Amundin, Mats; Laska, Matthias

doi:10.1093/chemse/bjs097

Cited by 71 publications

(48 citation statements)

References 47 publications

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“…This is emphatically not the case." However, these assertions are clearly at odds with the highly developed ability of mice and other mammals to discriminate an array of nonpheromonal chiral odorant enantiomeric pairs (23)(24)(25), with the divergent in vitro responses to enantiomers by different combinations of ORs (26) and, in particular, with the highly selective response of the musk-sensitive mouse receptor, MOR215-1, to (R)-muscone ("l-muscone") compared with (S)-muscone ("d-muscone") (27).…”

Section: Significancementioning

confidence: 99%

Implausibility of the vibrational theory of olfaction

Block

Jang

Matsunami

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

115

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The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. A previous study reported that human subjects differentiated hydrogen/ deuterium isotopomers (isomers with isotopic atoms) of the musk compound cyclopentadecanone as evidence supporting the theory. Here, we find no evidence for such differentiation at the molecular level. In fact, we find that the human musk-recognizing receptor, OR5AN1, identified using a heterologous OR expression system and robustly responding to cyclopentadecanone and muscone, fails to distinguish isotopomers of these compounds in vitro. Furthermore, the mouse (methylthio)methanethiol-recognizing receptor, MOR244-3, as well as other selected human and mouse ORs, responded similarly to normal, deuterated, and 13 C isotopomers of their respective ligands, paralleling our results with the musk receptor OR5AN1. These findings suggest that the proposed vibration theory does not apply to the human musk receptor OR5AN1, mouse thiol receptor MOR244-3, or other ORs examined. Also, contrary to the vibration theory predictions, muscone-d 30 lacks the 1,380-to 1,550-cm −1 IR bands claimed to be essential for musk odor. Furthermore, our theoretical analysis shows that the proposed electron transfer mechanism of the vibrational frequencies of odorants could be easily suppressed by quantum effects of nonodorant molecular vibrational modes. These and other concerns about electron transfer at ORs, together with our extensive experimental data, argue against the plausibility of the vibration theory.olfaction | isotopomers | cyclopentadecanone | muscone | electron transfer I n 1870, the British physician William Ogle wrote: "As in the eye and the ear the sensory impression is known to result not from the contact of material particles given off by the object seen or heard, but from waves or undulations of the ether or the air, one cannot but suspect that the same may be true in the remaining sense, and that the undulatory theory of smell. . . [may be] the true one" (1, 2). Of the 29 different "theories of odour" listed in the 1967 edition of The Chemical Senses (3), nine associate odor with vibrations, particularly those theories championed by Dyson (4, 5) and Wright (6-8). However, the premise that olfaction involves detection of vibrational frequencies of odorants remains highly speculative because neither the structures of the odorant receptors (ORs) nor the binding sites or the activation mechanisms triggered upon odorant binding to ORs have been established. In 1996-1997, Turin (9-12) elaborated on the undulatory theory of smell, as considered in more detail below, and suggested that a mechanism analogous to inelastic electron tunneling spectroscopy (13) may be involved, where tunneling electrons in the receptor probe the vibrational frequencies of odorants. In 2013, Gane et al. (14) In judging the plausibility...

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Section: Significancementioning

confidence: 99%

Implausibility of the vibrational theory of olfaction

Block

Jang

Matsunami

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

115

View full text Add to dashboard Cite

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“…Although most of the scientific evidence on odour reception collected in different species is well in agreement with this model, [10][11][12][13] it does not provide satisfactory explanation for the existence of many molecules of completely different chemical properties, i.e. size, shape, and functional groups, resulting in identical odours.…”

Section: Introductionmentioning

confidence: 88%

Testing odorant-receptor interaction theories in humans through discrimination of isotopomers

et al. 2017

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Odour reception takes place on the olfactory receptor neuron membrane, where molecular receptors interact with volatile odorant molecules. This interaction is classically thought to rely on chemical and structural features of the odorant, e.g. size, shape, functional groups. However, this model does not allow formulating a correct prediction for the smell of an odorant, suggesting that other molecular properties may play a role in the odour transduction process. An alternative model of olfaction maintains that odorant receptors can probe not only the structural and chemical features, but also the molecular vibration spectrum of the odorants. This constitutes the so-called vibration model of olfaction. According to this model, two isotopomers of the same molecule, i.e. two forms of the same molecule, one unaltered and one in which one or more hydrogen atoms are substituted with deuterium -which are therefore structurally and chemically identical, but with different molecular vibration spectra -would interact differently with an olfactory receptor, producing different olfactory perceptions in the brain. Here, we report on a duo-trio discrimination experiment conducted on human subjects, testing isotopomer pairs that have recently been shown to be differentially encoded in the honeybee brain.

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“…Briefly, each cell was lysed in buffer containing 0.1% NP-40, and reverse transcription was performed using SuperScript III (Invitrogen, Tokyo, Japan) and NotI-(dT) 18 primer in 6 μl scale. Artificial poly (A) tail was added at the 3′-end of the each cDNA using Terminal Deoxynucleotidyl Transferase (Roche, Tokyo, Japan).…”

Section: Rt-pcrmentioning

confidence: 99%

“…Each sample was PCR amplified using ExTaq (Takara Bio, Shiga, Japan) in two steps. NotI-(dT) 18 primer for the first step and gene-specific primers or the following degenerate primers against ORs for the second step were used in the combination of D1-D2, D3-D5, or D4-D5: D1, ACGGATCCATGGCCTAC-GACCGGTACGTN GCNATHTG; D2, ACCTCGAGTGGGAGGCGCAGGTGSWRAA NGCYTT; D3, ATGKSITWIGAYMGITWYGYIGC; D4, TWIGAYMGITWYGYIGCIRTITG; or D5, TAIAYIAIIGGRTT IAGCAWIGG.…”

Section: Rt-pcrmentioning

confidence: 99%

“…Smells of l-and d-menthol can be distinguished by mice and other mammals. 11,[17][18][19][20] In this study, we aimed to identify ORs that differentially recognized l-and d-menthol in mice. Since mice have over 1000 ORs, rather than random screening, we adopted a functional cloning strategy 21) in which the target ORs could be isolated from the OSNs that innervated the menthol-responsive glomeruli.…”

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confidence: 99%

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Enantioselective recognition of menthol by mouse odorant receptors

Tokura

Touhara

2015

Bioscience, Biotechnology, and Biochemistry

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The olfactory system has a remarkable ability to detect and discriminate a vast variety of odorant molecules. In mammals, hundreds to thousands of odorant receptors (ORs) expressed in olfactory sensory neurons play an essential role in this discrimination. Odorants are recognized by ORs in a combinatorial fashion in which a single odorant activates a particular combination of receptors, leading to its perception as a particular aroma. It is well known that enantiomers emit different aromas in spite of exhibiting otherwise identical chemical properties. To elucidate the molecular basis for the difference, we recorded responses to l- and d-menthol in the mouse olfactory bulb and found that enantiomers elicited similar but overlapping and distinct receptor activation patterns. We then identified l-menthol-specific and d-menthol-biased receptors and performed detailed structure–activity relationship studies, revealing high stereoselectivity of the enantiospecific menthol receptor. The binding site on ORs appears to have evolved to distinguish subtle differences in very similar odorant structures.

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Olfactory Discrimination Ability of Asian Elephants (Elephas maximus) for Structurally Related Odorants

Cited by 71 publications

References 47 publications

Implausibility of the vibrational theory of olfaction

Implausibility of the vibrational theory of olfaction

Testing odorant-receptor interaction theories in humans through discrimination of isotopomers

Enantioselective recognition of menthol by mouse odorant receptors

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