title: THE EVALUATION OF PEPTIDE/HISTIDINE TRANSPORTER 1 (PHT1) FUNCTION: UPTAKE KINETICS UTILIZING A COS-7 STABLY TRANSFECTED CELL LINE.
abstract: There have been relatively few studies focused on the proton-dependent oligopeptide transporter (POT) superfamily member, Peptide/Histidine Transporter 1 (PHT1), with respect to its contribution to the ADME of peptides and peptide-based drugs. These studies were conducted to determine hPHT1-mediated, H+-dependent uptake kinetics of histidine, carnosine, Gly-Sar and valacyclovir in stably transfected hPHT1-COS-7 cells comparative to kinetics determined in an empty vector (Mock) stably transfected cell line. The results suggest that Gly-Sar appears to be a substrate for PHT1 based on efflux from the stably transfected hPHT1 COS-7 cells. Histidine and Gly-Sar concentration- and time-dependent studies suggest mixed-uptake kinetics. These studies suggest that stably transfected hPHT1-COS-7 cells exhibit different uptake kinetics than those observed in our previous studies and illustrate the requirement for experiments to delineate the physiological role of hPHT1.
authors.affiliation: Department Industrial and Physical Pharmacy, College of Pharmacy, Nursing and Health Sciences, Purdue University, West Lafayette, IN, 47907, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lindley
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Carl
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Mowery
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Knipp
keywords: COS-7 cells; PHT1; Peptide transport; Peptide/Histidine Transporter 1; Proton-dependent Oligopeptide Transporter; Stable Transfection; Transporter Screening