Multidrug resistance (MDR) is a property of various cells associated with the capacity to reject or efflux a wide range of potentially harmful substances out of the cell. Pumps that effect such efflux are membrane proteins and belong to the ATP- binding cassette (ABC) superfamily. Among the members of the ABC family two are conferring MDR, P-glycoprotein (Pgp) and the multidrug resistance-associated protein (MRP1). In this study we investigated the functional activity of MDR transporters in olfactory mucosa of two species, rat and mouse. We used the fluorometric calcein-AM uptake assay on olfactory mucosal slices incubated with specific inhibitors of the MDR-transporters, verapamil and cyclosporin A as Pgp-inhibitors, and probenecid and MK571 as MRP-inhibitors. All four inhibitors caused significant increases in fluorescence intensities. To test if MDR transporters may be involved in the olfactory response we examined odorant evoked responses to single and mixed odorants by means of electro-olfactograms recordings (EOG). In the presence of the two MRP inhibitors, maximum EOG amplitudes were significantly reduced for all odorants tested, while Pgp inhibitors had only a moderate or no effect. Expression of Pgp and MRP1 encoding genes in the olfactory epithelium was further confirmed by RT-PCR. The results together suggest that MRP and Pgp transporters are present and functional in the main olfactory epithelium of rodents and are implicated in the olfactory response. The precise functional role in olfaction remains to be elucidated.
