title: Differential expression of organic cation transporters in normal and polyps human nasal epithelium: implications for in vitro drug delivery studies.
abstract: The aim of this study was to compare the expression of organic cation transporters (OCTs) in normal and polyps nasal epithelium. Primary cell cultures of human nasal epithelium (polyps and normal tissues) were compared by investigating the uptake of a fluorescent organic cation, [4-dimethylaminostyryl-N-methylpyridinium (4-Di-1-ASP)]. The effect of concentration, temperature, pH and competing inhibitors were investigated. Quantitative polymerase chain reaction (qPCR) was used to compare the OCTs gene expression levels in the cells. The K(m) (μM) and V(max) (μM/mg protein/15 min) for 4-Di-1-ASP uptake were higher in normal (K(m)=3031 ± 559.6, V(max)=70.8 ± 8.8) cells compared to polyps (K(m)=952.4 ± 207.8, V(max)=30.9 ± 2.1). qPCR results showed that OCT1-3 and organic cation/carnitine transporter 1-2 gene transcripts (OCTN1-2) were expressed in both normal and polyps cells at comparable levels, with OCT-3 having the highest expression level in both cultures. Kruskal-Wallis ANOVA showed that pH and specific inhibitors had similar effects on both normal and polyps cells (p>0.5). Similarly, OCTs and OCTNs gene expression levels were similar. This study showed that polyps biopsies can be used for isolating cells to study organic cation transporters in human nasal epithelium as no major functional or molecular differences relative to normal cells could be found.
authors.affiliation: Biopharmaceutics and Drug Delivery Laboratory, Dalhousie University, Halifax, NS B3H3J5, Canada. Remigius.agu@dal.ca
authors.forename: Remigius
authors.initials: R
authors.lastname: Agu
authors.forename: Chris
authors.initials: C
authors.lastname: MacDonald
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cowley
authors.forename: Di
authors.initials: D
authors.lastname: Shao
authors.forename: Ken
authors.initials: K
authors.lastname: Renton
authors.forename: David B
authors.initials: DB
authors.lastname: Clarke
authors.forename: Emad
authors.initials: E
authors.lastname: Massoud
mesh_terms: D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism*; D009298:Nasal Polyps / Q000378:metabolism* / Q000473:pathology; D027701:Organic Cation Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C032315:4-(4-dimethylaminostyryl)-1-methylpyridinium; D005456:Fluorescent Dyes; D027701:Organic Cation Transport Proteins; D011726:Pyridinium Compounds