Expression, localisation and functional implications of the transporter protein PEPT2 in the upper respiratory tract.
Infectious diseases of the upper respiratory tract are widespread and may initiate exacerbations of chronic respiratory diseases such as bronchial asthma or chronic obstructive pulmonary disease. Nebulisation of antibiotics as a topic treatment may lead to high local drug concentrations. To provide data on drug transport, the present study analysed a specific drug transport system on the molecular and functional level. Messenger RNA of the proton-coupled transporter PEPT2 that mediates physiological transport of oligopeptides as well as peptidomimetics like beta-lactams and aminolevulinic acid was discovered in rat nasal mucosa by RT-PCR. Real-time PCR studies indicated a lower expression level than control kidney samples. PEPT2 immunoreactivity was identified in nasal mucosa tissue. The protein was expressed in epithelial cells, but goblet cells did not exhibit PEPT2 expression. Functional studies with rat preparations led to uptake of a fluorophore-conjugated substrate into epithelial cells of nasal mucosa. Goblet cells did not exhibit uptake activity. The uptake was competitively inhibited by dipeptides demonstrating similar substrate specificity as reported for PEPT2. Together, these data suggest that PEPT2 is likely to play an important role in mucosal peptide metabolism and may represent a novel target for therapeutic efforts in upper airway diseases.
Quarcoo
David
D
Institute of Occupational Medicine, Charite - Universitatsmedizin Berlin, Free University and Humboldt University, Berlin, Germany.
Fischer
Tanja C
TC
Heppt
Werner
W
Lauenstein
Hans-Dieter
HD
Pilzner
Carolin
C
Welte
Tobias
T
Groneberg
David A
DA
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000627:therapeutic use; D003374:Coumarins / Q000378:metabolism; D015870:Gene Expression; D009842:Oligopeptides / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000378:metabolism*; D012141:Respiratory Tract Infections / Q000188:drug therapy; D027981:Symporters / Q000378:metabolism*
D000891:Anti-Infective Agents, Local; D003374:Coumarins; D009842:Oligopeptides; D012333:RNA, Messenger; D027981:Symporters; C118033:alanyl-lysyl-amca; C093694:hydrogen-coupled oligopeptide transporter PepT2