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Pharm Res. 2017 Dec;34(12):2488-2497. doi: 10.1007/s11095-017-2234-z. Epub 2017 Aug 22.

Oligopeptide Transport in Rat Lung Alveolar Epithelial Cells is Mediated by Pept2.

Gukasyan HJ1,2, Uchiyama T1,3, Kim KJ1,4,5,6,7, Ehrhardt C8, Wu SK1,9, Borok Z4,5,10, Crandall ED4,5,11,12, Lee VHL13,14.

Author information

1
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.
2
Allergan plc, Irvine, California, USA.
3
Oozora Pharmacy, Hamamatsu, Shizuoka, Japan.
4
Will Rogers Institute Pulmonary Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
5
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
6
Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
7
Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, California, USA.
8
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
9
Amgen, Inc., Thousand Oaks, California, USA.
10
Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
11
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
12
Mork Family Department of Chemical Engineering and Materials Science, Viterbi School of Engineering, University of Southern California, Los Angeles, California, USA.
13
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA. vincent.lee@cuhk.edu.hk.
14
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, 8/F, Lo Kwee-Seong Integrated Biomedical Sciences Building, Area 39, Shatin, N.T. Hong Kong SAR, China. vincent.lee@cuhk.edu.hk.

Abstract

PURPOSE:

Studies were conducted in primary cultured rat alveolar epithelial cell monolayers to characterize peptide transporter expression and function.

METHODS:

Freshly isolated rat lung alveolar epithelial cells were purified and cultured on permeable support with and without keratinocyte growth factor (KGF). Messenger RNA and protein expression of Pept1 and Pept2 in alveolar epithelial type I- and type II-like cell monolayers (±KGF, resp.) were examined by RT-PCR and Western blotting. 3H-Glycyl-sarcosine (3H-gly-sar) transmonolayer flux and intracellular accumulation were evaluated in both cell types.

RESULTS:

RT-PCR showed expression of Pept2, but not Pept1, mRNA in both cell types. Western blot analysis revealed presence of Pept2 protein in type II-like cells, and less in type I-like cells. Bi-directional transmonolayer 3H-gly-sar flux lacked asymmetry in transport in both types of cells. Uptake of 3H-gly-sar from apical fluid of type II-like cells was 7-fold greater than that from basolateral fluid, while no significant differences were observed from apical vs. basolateral fluid of type I-like cells.

CONCLUSIONS:

This study confirms the absence of Pept1 from rat lung alveolar epithelium in vitro. Functional Pept2 expression in type II-like cell monolayers suggests its involvement in oligopeptide lung disposition, and offers rationale for therapeutic development of di/tripeptides, peptidomimetics employing pulmonary drug delivery.

KEYWORDS:

SLC15; alveolar epithelial cell monolayer; carrier-mediated transport; di/tripeptide; pulmonary drug disposition

PMID:
28831683
DOI:
10.1007/s11095-017-2234-z
[Indexed for MEDLINE]

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