Abstract
With nearly 400 members, the solute-linked carrier (SLC) superfamily is one of the most important gene classes concerning the disposition of drugs and the transport of physiological substrates in the human body. The mapping of related transport proteins is already well advanced for the intestines, kidneys and liver, but it has recently been brought into focus for various respiratory epithelia. The aim of this study was to evaluate the expression of several SLC transporters in differently cultured RPMI 2650 cells, as well as in specimens of the human nasal mucosa. The expression profiles of PEPT2, OATP1A2, OATP4C1, OCT2, OCTN1 and OCTN2 were investigated at the gene and protein levels by performing RT-PCR, western blot analysis and immunohistological staining. Uptake assays using appropriate substrates and inhibitory substances were performed to compare the activity of peptide, organic anion and organic cation transporters, respectively, among the three models. Expression of the six SLC transporters under investigation was confirmed at the mRNA and protein levels in human nasal mucosa ex vivo as well as in RPMI 2650 cells grown under different culture conditions. The functionality was almost equal among all of the models for the PEPT and OCT(N) transporters, while the functional activity of the OATP transporters was more pronounced for both in vitro models than for excised nasal tissue. Despite negligible variations in transporter capacities, the RPMI 2650 cell cultures and freshly isolated human nasal epithelium showed nearly comparable expression patterns for the examined SLC proteins. Therefore, in vitro models based on the RPMI 2650 cell line could provide helpful data during the preclinical investigation of intranasally administered drug formulations and in the development of strategies to target nasal drug transporters for either local or systemic drug delivery.