Human proton/oligopeptide transporter (POT) genes: Identification of putative human genes using bioinformatics
Journal Title: The AAPS Journal - Year 2000, Vol 2, Issue 2
Abstract
Purpose: The proton-dependent oligopeptide transporters (POT) gene family currently consists of ∼70 cloned cDNAs derived from diverse organisms. In mammals, two genes encoding peptide transporters, PepT1 and PepT2 have been cloned in several species including humans, in addition to a rat histidine/peptide transporter (rPHT1). Because the Candida elegans genome contains five putative POT genes, we searched the available protein and nucleic acid databases for additional mammalian/human POT genes, using iterative BLAST runs and the human expressed sequence tags (EST) database. The apparent human orthologue of rPHT1 (expression largely confined to rat brain and retina) was represented by numerous ESTs originating from many tissues. Assembly of these ESTs resulted in a contiguous sequence covering ∼95% of the suspected coding region. The contig sequences and analyses revealed the presence of several possible splice variants of hPHT1. A second closely related human EST-contig displayed high identity to a recently cloned mouse cDNA encoding cyclic adenosine monophosphate (cAMP)-inducible 1 protein (gi:4580995). This contig served to identify a PAC clone containing deduced exons and introns of the likely human orthologue (termed hPHT2). Northern analyses with EST clones indicated that hPHT1 is primarily expressed in skeletal muscle and spleen, whereas hPHT2 is found in spleen, placenta, lung, leukocytes, and heart. These results suggest considerable complexity of the human POT gene family, with relevance to the absorption and distribution of cephalosporins and other peptoid drugs.
Authors and Affiliations
Christopher W. Botka, Thomas W. Wittig, Richard C. Graul, Carsten Uhd Nielsen, Wolfgang Sadée, Kazutaka Higaki, Gordon L. Amidon
Keywords
Related Articles
- EP ID EP682089
- DOI 10.1208/ps020216
- Views 95
- Downloads 0
Toward the prediction of CNS drug-effect profiles in physiological and pathological conditions using microdialysis and mechanism-based pharmacokinetic-pharmacodynamic modeling
Our ultimate goal is to develop mechanism-based pharmacokinetic (PK)-pharmacodynamic (PD) models to characterize and to predict CNS drug responses in both physiologic and pathologic conditions. To this end, it is essenti...
Mucoadhesive Microspheres for Gastroretentive Delivery of Acyclovir: In Vitro and In Vivo Evaluation
The aim of the present investigation was to evaluate the potential use of mucoadhesive microspheres for gastroretentive delivery of acyclovir. Chitosan, thiolated chitosan, Carbopol 71G and Methocel K15M were used as muc...
Characterization of the distribution, polymorphism, and stability of nimodipine in its solid dispersions in polyethylene glycol by micro-Raman spectroscopy and powder x-ray diffraction
In the present study, a series of solid dispersions of the drug nimodipine using polyethylene glycol as carrier were prepared following the hot-melt method. Micro-Raman spectroscopy in conjunction with X-ray powder diffr...
Epigenetic Modifications of Nrf2 by 3,3′-diindolylmethane In Vitro in TRAMP C1 Cell Line and In Vivo TRAMP Prostate Tumors
The online version of this article (doi:10.1208/s12248-013-9493-3) contains supplementary material, which is available to authorized users.
Ocular Drug Delivery
Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aq...