Glutathione conjugation of the rabbit mammary pheromone 2-methylbut-2-enal

International audienceIn the process of smell, the olfactory signal is initiated by the binding of odorous molecules to olfactory receptors. In the receptor environment,associated events are supposed to modulate this signal.Thus, the xenobiotic metabolizing enzymes, potentially involved in the clearance of the odorous molecules, could modulate the availability of these molecules for the olfactory receptors, and consequently could participate indirectly in the olfactory signal termination. A mammary pheromone, which is an odorous aldehyde (2-methylbut-2-enal or 2MB2) has been recently characterized in the rabbit by our group. The aim of this work was to elucidate the metabolism of 2MB2 in the rabbit olfactory mucosa (OM). Results of in vitro studies demonstrate that 2MB2 is conjugated to glutathione in OM, and that this metabolism is much stronger than in the liver. Besides, 2MB2 is less conjugated to glutathione in newborn rabbit OM than in weanling or adult animal mucosa. This last result is correlated with age-related variations in the expression of different olfactory glutathione transferase isoforms. In addition to in vitro studies, we developed an ex-vivo method in order to evaluate the metabolism of 2MB2 in a whole-tissue sample. This approach allows the nasal cavity to keep its complex structure, which is necessary for the olfactory physiological process. The disappearance of the volatile aldehyde is measured in the headspace around the isolated nasal cavity put in a closed vial, enabling a global measurement of the pheromone metabolism. These results demonstrate that 2MB2 is metabolized by the rabbit olfactory mucosa especially as glutathione conjugates, and suggest the use of this pheromone as an interesting tool for further investigations on the possible involvement of the xenobiotic metabolizing enzymes in the process of smell