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

Manar Al-Ghabeish; Todd Scheetz; Mahfoud Assem; Maureen D Donovan

doi:10.1021/acs.molpharmaceut.5b00103

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

Journal article

Open access

Peer reviewed

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

Manar Al-Ghabeish, Todd Scheetz, Mahfoud Assem and Maureen D Donovan

Molecular pharmaceutics, Vol.12(8), pp.2742-2754

08/03/2015

DOI: 10.1021/acs.molpharmaceut.5b00103

PMCID: PMC4671632

PMID: 26106909

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https://www.ncbi.nlm.nih.gov/pmc/articles/4671632View

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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.

Administration, Intranasal

Animals

Biological Transport - genetics

Cattle

Gene Expression Profiling

Humans

Mice

Multidrug Resistance-Associated Proteins - genetics

Nasal Absorption - genetics

Nasal Mucosa - metabolism

Nucleoside Transport Proteins - genetics

Oligonucleotide Array Sequence Analysis

Organic Cation Transport Proteins - genetics

Rats

Species Specificity

Details

Title: Subtitle: Microarray Determination of the Expression of Drug Transporters in Humans and Animal Species Used for the Investigation of Nasal Absorption
Creators: Manar Al-Ghabeish - University of Iowa
Todd Scheetz - University of Iowa
Mahfoud Assem - University of Iowa
Maureen D Donovan - University of Iowa
Resource Type: Journal article
Publication Details: Molecular pharmaceutics, Vol.12(8), pp.2742-2754
DOI: 10.1021/acs.molpharmaceut.5b00103
PMID: 26106909
PMCID: PMC4671632
NLM abbreviation: Mol Pharm
ISSN: 1543-8384
eISSN: 1543-8392
Grant note: R01DC08374 / NIDCD NIH HHS R01 DC008374 / NIDCD NIH HHS P30 ES005605 / NIEHS NIH HHS
Language: English
Date published: 08/03/2015
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Ophthalmology and Visual Sciences
Record Identifier: 9984366023402771

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