6533b837fe1ef96bd12a3494

RESEARCH PRODUCT

Expression and differential localization of xenobiotic transporters in the rat olfactory neuro-epithelium.

Yves ArturChristine BelloirNicolas ThiebaudAnne-marie Le BonJean-marie HeydelFranck MénétrierAnne-laure MinnFabrice Neiers

subject

Male[ SDV.AEN ] Life Sciences [q-bio]/Food and NutritionMESH : Multidrug Resistance-Associated Proteinsp glycoproteinATP-binding cassette transporterMESH : HepatocytesReceptors OdorantMESH : P-GlycoproteinMESH: HepatocytesMESH : Lymphatic Vessels0302 clinical medicineMESH : Protein Transportugt2a1MESH: SmellMESH: Receptors OdorantMESH: AnimalsReceptorxenobiotic metabolizingmucosa0303 health sciencesMESH : Gene Expression RegulationMESH : RatsGeneral NeuroscienceMESH : OdorsMESH: Gene Expression RegulationSmellProtein Transportmedicine.anatomical_structureBiochemistryLivertransporterbarrierEffluxMultidrug Resistance-Associated ProteinsMESH: Multidrug Resistance-Associated ProteinsMESH: XenobioticsMESH: Protein TransportMESH: P-GlycoproteinMESH: RatsMESH: Lymphatic VesselsMESH : Maleodorant clearancebrainMESH : XenobioticsxenobioticBiologysystemMESH : Rats WistarOlfactory Receptor NeuronsXenobiotics03 medical and health sciencesbulbOlfactory Mucosamultidrug resistanceMESH : Receptors OdorantmedicineAnimalsATP Binding Cassette Transporter Subfamily B Member 1Rats WistardetoxificationMESH: Olfactory Mucosa030304 developmental biologyLymphatic VesselsMESH : Olfactory MucosaMESH: OdorsMESH : LiverTransporterMESH: Rats WistarMESH: Olfactory Receptor NeuronsEpitheliumMESH: MaleOlfactory bulbRatsenzymeGene Expression RegulationOdorantsHepatocytesMESH : SmellMESH : Olfactory Receptor NeuronsMESH : Animalsolfactory epitheliumOlfactory epitheliumperireceptor event[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition030217 neurology & neurosurgeryDrug metabolismMESH: Liver

description

International audience; Transporters, such as multidrug resistance P-glycoproteins (MDR), multidrug resistance-related proteins (MRP) and organic anion transporters (OATs), are involved in xenobiotic metabolism, particularly the cellular uptake or efflux of xenobiotics (and endobiotics) or their metabolites. The olfactory epithelium is exposed to both inhaled xenobiotics and those coming from systemic circulation. This tissue has been described as a pathway for xenobiotics to the brain via olfactory perineural space. Thereby, olfactory transporters and xenobiotic metabolizing enzymes, dedicated to the inactivation and the elimination of xenobiotics, have been involved in the toxicological protection of the brain, the olfactory epithelium itself and the whole body. These proteins could also have a role in the preservation of the olfactory sensitivity by inactivation and clearance of the excess of odorant molecules from the perireceptor space. The goal of the present study was to increase our understanding of the expression and the localization of transporters in this tissue. For most of the studied transporters, we observed an opposite mRNA expression pattern (RT-PCR) in the olfactory epithelium compared to the liver, which is considered to be the main metabolic organ. Olfactory epithelium mainly expressed efflux transporters (MRP, MDR). However, a similar pattern was observed between the olfactory epithelium and the olfactory bulb. We also demonstrate distinct cellular immunolocalization of the transporters in the olfactory epithelium. As previously reported, Mrp1 was mainly found in the supranuclear portions of supporting cells. In addition, Mrp3 and Mrp5 proteins, which were detected for the first time in olfactory epithelium, were localized to the olfactory neuron layer, while Mdr1 was localized to the capillary endothelium of lymphatic vessels in the subepithelial region. The pattern of expression and the distinct localization of the olfactory transporters showed in this work may highlight on their specific function in the whole olfactory epithelium.

10.1016/j.neulet.2011.10.018https://hal.archives-ouvertes.fr/hal-00755577