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. 2017 Aug 31;7(1):10219.
doi: 10.1038/s41598-017-10080-z.

Odorant-odorant metabolic interaction, a novel actor in olfactory perception and behavioral responsiveness

Hassan-Ismail Hanser  1 , Philippe Faure  1 , Aline Robert-Hazotte  1 , Yves Artur  1 , Patricia Duchamp-Viret  2 , Gérard Coureaud  3 , Jean-Marie Heydel  4
Affiliations

Odorant-odorant metabolic interaction, a novel actor in olfactory perception and behavioral responsiveness

Hassan-Ismail Hanser et al. Sci Rep. .

Abstract

In the nasal olfactory epithelium, olfactory metabolic enzymes ensure odorant clearance from the olfactory receptor environment. This biotransformation of odorants into deactivated polar metabolites is critical to maintaining peripheral sensitivity and perception. Olfactory stimuli consist of complex mixtures of odorants, so binding interactions likely occur at the enzyme level and may impact odor processing. Here, we used the well-described model of mammary pheromone-induced sucking-related behavior in rabbit neonates. It allowed to demonstrate how the presence of different aldehydic odorants efficiently affects the olfactory metabolism of this pheromone (an aldehyde too: 2-methylbut-2-enal). Indeed, according to in vitro and ex vivo measures, this metabolic interaction enhances the pheromone availability in the epithelium. Furthermore, in vivo presentation of the mammary pheromone at subthreshold concentrations efficiently triggers behavioral responsiveness in neonates when the pheromone is in mixture with a metabolic challenger odorant. These findings reveal that the periphery of the olfactory system is the place of metabolic interaction between odorants that may lead, in the context of odor mixture processing, to pertinent signal detection and corresponding behavioral effect.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
In vitro Glutathione conjugation of 2MB2 in presence of challengers. Glutathione conjugation of 2MB2 was determined by HPLC measurement, after incubation during 80 min at 37 °C of 2MB2 + reduced glutathione in presence of OE homogenate from newborn rabbits. 2MB2 enzymatic glutathione conjugation was compared to those obtained in presence of a challenger compound at equimolar concentration (ratio 1:1, A) and 3 times more concentrated (ratio 1:3, B). Results are expressed as % of the glutathione-2MB2 conjugate amount; 100% being obtained for 2MB2 alone. The % are means of n = 3–5 replicated measures ± SEM. *, ** and *** indicate significant differences (p ≤ 0.05, p ≤ 0.01 and p ≤ 0.001 respectively) between the control (2MB2 alone) and mixture conditions (Kruskal-Wallis multiple comparisons followed by a Conover-Iman post-hoc test). Odorant abbreviations: 2MB2: 2-methylbut-2-enal (the mammary pheromone), 2MP2: 2-methylpent-2-enal, Cinnam: Cinnamaldehyde, EA: ethyl acetate.
Figure 2
Figure 2
Ex vivo metabolism of gaseous 2MB2 in presence of challengers. Kinetic of disappearance of 2MB2 alone (cross), during the first 30 min, in presence of a total freshly collected newborn rabbit’s OE, compared to those obtained for 2MB2 mixed with 2MP2 (A), 3MB2 (B) or EA (C). Each mixture was tested at equimolar concentration (ratio 1:1; empty triangle) and with three times more concentrated challenger (ratio 1:3; solid triangle). The 2MB2 amount was determined, every 5 min by headspace gas chromatography measurement and 2MB2 peak integration analysis. Results plotted here are expressed as a percentage of 2MB2 in the headspace, relative to the initial amount 100% measured at 5 min for n = 3–8 replicates ± SEM. ** and *** indicate significant differences (p ≤ 0.01 and p ≤ 0.001 respectively) between the control (2MB2 alone) and binary mixtures conditions (Kruskal-Wallis multiple comparisons followed by a Conover-Iman post-hoc test). Same odorant abbreviations as in Fig. 1.
Figure 3
Figure 3
Behavioral responsiveness to 2MB2 alone or in binary mixture with 2MP2, 3MB2 or EA. Proportions of rabbit pups responding by orocephalic movements to different stimuli in the glass-rod test (n = 15 to 36 pups, from 3 to 7 litters depending on the groups). (A–C) Responsiveness to 2MB2 (the mammary pheromone) at 10−6 g/ml and 10−9 g/ml, illustrating positive and negative controls, compared to responsiveness to 2MP2 (A), 3MB2 (B) and EA (C) each singly presented at 10-6 g/ml, or at 10−9 g/ml in binary mixture with 2MB2. D: responsiveness to 2MB2 (10−9 g/ml) + 2MP2 (10−6 g/ml) mixture compared to three other mixtures containing the same concentration of 2MB2 (10−9 g/ml) and decreasing concentrations of 2MP2 (10−7 10−8, 10−9 g/ml). Within each graph, distinct digits indicate statistical differences (p ≤ 0.05): χ² or Cochran test, for independent or dependent multiple comparisons, respectively, followed by a McNemar or χ² test for pairwise comparisons. Same odorant abbreviations as in Fig. 1.
Figure 4
Figure 4
Ex vivo EOG responses to single odorants and binary mixtures including 2MB2. (A,B) Representative examples of EOGs (raw recordings). (A) EOGs recorded in response to 2MB2, 2MP2 and their binary mixtures at different concentrations (see Table 1). (B) EOGs recorded in response to 2MB2, EA and their binary mixtures at different concentrations (see Table 1). (C,D) EOG amplitudes are given as mean ± SEM averaged for the three recording sites and 3–5 repeated stimulations, for each stimulating condition. (C) Responses to single odorants; D: responses for binary mixtures. In each histogram, stimuli are sorted from the left to the right according to increasing calculated concentrations (see Table 1). Within each graph, distinct digits indicate statistical differences (p ≤ 0.05, Kruskal-Wallis multiple comparisons followed by a Conover-Iman post-hoc test). Same odorant abbreviations as in Fig. 1.
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