title: Membrane transporters.
abstract: Carrier-mediated drug transport is relatively unexplored in comparison with passive transcellular and paracellular drug transport. Yet, there is a host of transporter proteins that can be targeted for improving epithelial drug absorption. Generally, these are transport mechanisms for amino acids, dipeptides, monosaccharides, monocarboxylic acids, organic cations, phosphates, nucleosides, and water-soluble vitamins. Among them, the dipeptide transporter mechanism has received the most attention. Dipeptide transporters are H(+)-coupled, energy-dependent transporters that are known to play an essential role in the oral absorption of beta-lactam antibiotics, angiotensin-converting enzyme (ACE) inhibitors, renin inhibitors, and an anti-tumor drug, bestatin. Moreover, several investigators have demonstrated the utility of the dipeptide transporter as a platform for improving the oral bioavailability of drugs such as zidovudine and acyclovir through dipeptide prodrug derivatization. Thus far, at least four proton-coupled peptide transporters have been cloned. The first one cloned was PepT1 from the rabbit small intestine. The focus of this presentation will be structure-function, intracellular trafficking, and regulation of PepT1. Disease, dietary, and possible excipient influences on PepT1 function will also be discussed.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, PSC 708, Los Angeles, CA 90089-9121, USA. vincentL@hsc.usc.edu
authors.forename: V H
authors.initials: VH
authors.lastname: Lee
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000493:pharmacokinetics*; D002462:Cell Membrane / Q000378:metabolism; D004151:Dipeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D000074011:Peptide Transporter 1; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D027981:Symporters
chemical_list: D002352:Carrier Proteins; D004151:Dipeptides; D000074011:Peptide Transporter 1; C082186:SLC15A1 protein, human; D027981:Symporters