title: Microarray Determination of the Expression of Drug Transporters in Humans and Animal Species Used for the Investigation of Nasal Absorption.
abstract: Mice and rats are commonly used to investigate in vivo nasal drug absorption, yet their small nasal cavities limit their use for in vitro investigations. Bovine tissue explants have been used to investigate drug transport through the nasal respiratory and olfactory mucosae, yet limited information is available regarding the similarities and differences among these animal models compared to humans. The aim of this study was to compare the presence of a number of important drug transporters in the nasal mucosa of these species. DNA microarray results for nasal samples from humans, rats, and mice were obtained from GenBank, while DNA microarray and RT-PCR were performed on bovine nasal explants. The drug transporters of interest include multidrug resistance, cation, anion, peptide, and nucleoside transporters. Each of the species (mouse, rat, cattle, and human) shows similar patterns of expression for most of the important drug transporters. Several transporters were highly expressed in all the species, including MRP1, OCTN2, PEPT2, and y+LAT2. While some differences in transporter mRNA and protein expression were observed, the transporter expression patterns were quite similar among the species. The differences suggest that it is important to be aware of any specific differences in transporter expression for a given compound being investigated, yet the similarities support the continued use of these animal models during preclinical investigation of intranasally administered therapeutics.
authors.affiliation: †Division of Pharmaceutics and Translational Therapeutics, University of Iowa, Iowa City, Iowa 52242, United States.
authors.forename: Manar
authors.initials: M
authors.lastname: Al-Ghabeish
authors.affiliation: ‡Department of Biomedical Engineering, Department of Ophthalmology and Visual Sciences, and Center for Bioinformatics and Computational Biology, University of Iowa, Iowa City, Iowa 52242, United States.
authors.forename: Todd
authors.initials: T
authors.lastname: Scheetz
authors.affiliation: †Division of Pharmaceutics and Translational Therapeutics, University of Iowa, Iowa City, Iowa 52242, United States.
authors.forename: Mahfoud
authors.initials: M
authors.lastname: Assem
authors.affiliation: †Division of Pharmaceutics and Translational Therapeutics, University of Iowa, Iowa City, Iowa 52242, United States.
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Donovan
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002417:Cattle; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D065588:Nasal Absorption / Q000235:genetics*; D009297:Nasal Mucosa / Q000378:metabolism; D033703:Nucleoside Transport Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D051381:Rats; D013045:Species Specificity
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; D033703:Nucleoside Transport Proteins; D027701:Organic Cation Transport Proteins
keywords: RT-PCR; animal models; drug transporters; microarray; nasal mucosa