Microarray Determination of the Expression of Drug Transporters in Humans and Animal Species Used for the Investigation of Nasal Absorption

Abstract

Purpose 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. Methods 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. Results Each of the species (mouse, rat, cow 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. Conclusion 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.

The role of L-type amino acid transporters in the uptake of glyphosate across mammalian epithelial tissues

“…Previous investigators have shown that LAT1 and LAT2 are expressed in Caco-2 cells, and confirmation of the expression of these transporters throughout the intestinal tract of animals and humans has been reported (Fraga et al, 2005;Terada et al, 2005). The expression of LAT1 and LAT2 gene transcripts in the nasal olfactory and respiratory mucosa of humans, rats and cattle was recently reported by Al Ghabeish et al (2015) using DNA microarray analysis. Weak expression of LAT1 in cattle mucosal tissues was reported by Zhang (2009) using immunoblotting, andFerreira andDonovan (2013) more recently reported the confirmation of the expression and localization of LAT2 in cattle nasal mucosa using both PCR and immunohistochemical analyses.…”

Pharmacokinetic Interaction between Naloxone and Naltrexone Following Intranasal Administration to Healthy Subjects

“…Human nasal epithelial cells have appreciable levels of OCT3, OCTN1, and OCTN2 with a minor amount of OCT1 (Shao et al, 2013). They also express P-glycoprotein, several members of the multidrug resistance-associated family, and organic anion and peptide transporters (Al-Ghabeish et al, 2015). Neither naloxone nor naltrexone is a substrate for P-glycoprotein (Mahar Doan et al, 2002;Kanaan et al, 2009).…”

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