[Drug transport in the respiratory epithelium].

Paul, H B; Welte, T; Groneberg, D A

The aerosolic administration of peptidomimetic drugs with a peptide backbone may play a crucial role in the future treatment of diseases. Especially rational drug design offers an option to synthesize new drugs that are carried by specific drug transporters. Out of the presently identified transporter proteins PEPT1 and PEPT2, the high-affinity transporter PEPT2 is found in the respiratory tract. The transporter possess 12 membrane spanning domains and catalyses an electrogenic uphill drug transport using a transmembrane electrochemical proton gradient. PEPT2 is expressed in the bronchial epithelium and in alveolar type II pneumocytes in human airways. Kinetic studies demonstrated that peptidomimetic compounds including antibiotic, antiviral and antineoplastic drugs are carried by PEPT2. The transporter also carries delta-aminolevulinic acid into the airways. This molecule can be used for the diagnostics of pulmonary neoplasms and for photodynamic therapy. Using the recently published data on minimal structural requirements for PEPT2-substrates, rational drug design may lead to a new generation of respiratory drugs and prodrugs, which are delivered to the airways via the molecular mechanisms of the PEPT2 transport system.