Dual capacity of a human olfactory receptor

Spehr, Marc; Schwane, Katlen; Heilmann, Stefan; Gisselmann, Günter; Hummel, Thomas; Hatt, Hanns

doi:10.1016/j.cub.2004.09.034

Cited by 64 publications

(35 citation statements)

References 5 publications

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“…In addition, some ORs might be highly conserved because they are also expressed in other tissues (e.g. OR17-4 in sperm, [89]). In any event, we will still need bioassays of candidate molecules discovered in this or other ways.…”

Section: (D) Methods For Narrowing Down the Candidate Molecules For Bmentioning

confidence: 99%

The search for human pheromones: the lost decades and the necessity of returning to first principles

Wyatt

2015

Proc. R. Soc. B.

119

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As humans are mammals, it is possible, perhaps even probable, that we have pheromones. However, there is no robust bioassay-led evidence for the widely published claims that four steroid molecules are human pheromones: androstenone, androstenol, androstadienone and estratetraenol. In the absence of sound reasons to test the molecules, positive results in studies need to be treated with scepticism as these are highly likely to be false positives. Common problems include small sample sizes, an overestimate of effect size (as no effect can be expected), positive publication bias and lack of replication. Instead, if we are to find human pheromones, we need to treat ourselves as if we were a newly discovered mammal, and use the rigorous methods already proven successful in pheromone research on other species. Establishing a pheromone relies on demonstration of an odour-mediated behavioural or physiological response, identification and synthesis of the bioactive molecule(s), followed by bioassay confirmation of activity. Likely sources include our sebaceous glands. Comparison of secretions from adult and pre-pubertal humans may highlight potential molecules involved in sexual behaviour. One of the most promising human pheromone leads is a nipple secretion from the areola glands produced by all lactating mothers, which stimulates suckling by any baby not just their own.

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Section: (D) Methods For Narrowing Down the Candidate Molecules For Bmentioning

confidence: 99%

The search for human pheromones: the lost decades and the necessity of returning to first principles

Wyatt

2015

Proc. R. Soc. B.

119

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“…A primarily configural representation of odour mixture might indeed result from molecular competition at a single olfactory receptor level where elements could act both as agonists and antagonists (Spehr et al, 2004;Sanz et al, 2008). Configural processing may also occur as soon as mixture components activate a set of significantly overlapping receptors (Jinks and Laing, 1999;Kay et al, 2003).…”

Section: G Coureaud and Othersmentioning

confidence: 99%

Elemental and configural processing of odour mixtures in the newborn rabbit

Coureaud

Hamdani

Schaal

et al. 2009

Journal of Experimental Biology

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SUMMARYThe processing of odour mixtures by young organisms is poorly understood. Recently, the perception of an AB mixture, known to engage configural perception in adult humans, was suggested also to be partially configural in newborn rabbits. In particular, pups did not respond to AB after they had learned A or B. However, two alternative hypotheses might be suggested to explain this result: the presence in the mixture of a novel odorant that inhibits the response to the learned stimulus, and the unevenness of the sensory and cognitive processes engaged during the conditioning and the behavioural testing. We conducted four experiments to explore these alternative hypotheses. In experiment 1, the learning of A or B ended in responses to mixtures including a novel odorant (AC or BC). Experiment 2 pointed to the absence of overshadowing. Therefore, a novelty effect cannot explain the non-response to AB after the learning of A or B. In experiment 3, pups having learned A or B in AC or BC did not respond to AB. However, they generalized odour information acquired in AB to AC or BC in experiment 4. Thus, the balancing of the perceptual tasks between the conditioning and retention test does not enhance the response to the AB mixture. To sum up, the present experiments give concrete support to the partially configural perception of specific odour mixtures by newborn rabbits.

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“…Beginning in 2000, ORs have been repeatedly reported also to be expressed in non-olfactory tissues (De la Cruz et al 2009;Feldmesser et al 2006;Zhang et al 2007) where they play additional roles. Some ORs govern sperm chemotaxis (Fukuda and Touhara 2006;Spehr et al 2004), inhibit prostate cancer cell proliferation (Neuhaus et al 2009), regulate cell migration and adhesion in muscle (Griffin et al 2009), and regulate serotonin secretion of gastro-intestinal cells (Braun et al 2007;Kidd et al 2008). ORs are also reported to be tumor markers (Leja et al 2009;Weng et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Modeling of mammalian olfactory receptors and docking of odorants

et al. 2012

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Olfactory receptors (ORs) belong to the superfamily of G protein-coupled receptors (GPCRs), the second largest class of genes after those related to immunity, and account for about 3 % of mammalian genomes. ORs are present in all multicellular organisms and represent more than half the GPCRs in mammalian species (e.g., the mouse OR repertoire contains >1,000 functional genes). ORs are mainly expressed in the olfactory epithelium where they detect odorant molecules, but they are also expressed in a number of other cells, such as sperm cells, although their functions in these cells remain mostly unknown. It has recently been reported that ORs are present in tumoral tissues where they are expressed at different levels than in healthy tissues. A specific OR is overexpressed in prostate cancer cells, and activation of this OR has been shown to inhibit the proliferation of these cells. Odorant stimulation of some of these receptors results in inhibition of cell proliferation. Even though their biological role has not yet been elucidated, these receptors might constitute new targets for diagnosis and therapeutics. It is important to understand the activation mechanism of these receptors at the molecular level, in particular to be able to predict which ligands are likely to activate a particular receptor ('deorphanization') or to design antagonists for a given receptor. In this review, we describe the in silico methodologies used to model the three-dimensional (3D) structure of ORs (in the more general framework of GPCR modeling) and to dock ligands into these 3D structures.

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Dual capacity of a human olfactory receptor

Cited by 64 publications

References 5 publications

The search for human pheromones: the lost decades and the necessity of returning to first principles

The search for human pheromones: the lost decades and the necessity of returning to first principles

Elemental and configural processing of odour mixtures in the newborn rabbit

Modeling of mammalian olfactory receptors and docking of odorants

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