ISSN:
1573-904X
Keywords:
peptide transporters
;
chimeras
;
intestinal absorption
;
renal reabsorption
;
β-lactam antibiotics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Purpose. Peptide transporters PEPT1 and PEPT2 differ substantiallyin their substrate affinity and recognition. The aim of this study is todefine the structural domains which influence the functionalcharacteristics of both transporters Methods. Two kinds of chimeric peptide transporters (PEPT-N1C2and PEPT-N2C1) were constructed, and their functional characteristicswere compared with those of wild-type transporters in stabletransfectants. Results. PEPT-N1C2, the N-terminal half of rat PEPT1 and theC-terminal half of rat PEPT2, and the reciprocal chimera PEPT-N2C1were functionally expressed in LLC-PK1 cells. The pH-profiles of [14C]glycylsarcosine uptake by PEPT-N1C2 and PEPT-N2C1 were close tothose of PEPT1 and PEPT2, respectively. Substrate recognition forPEPT-N1C2 and PEPT-N2C1 was also similar to that of PEPT1 andPEPT2, respectively. However, substrate affinities for PEPT-N1C2were higher than those for PEPT1, although those for PEPT-N2C1 andPEPT2 were comparable. Conclusions. These results indicate that functional regions which areassociated with the extracellular pH changes and are responsible forsubstrate recognition of PEPT1 and PEPT2 may be located in theN-terminal halves of the proteins. In addition, it is suggested that thedomain to affect the substrate affinity exists in the C-terminal as wellas in the N-terminal half of rat PEPT2.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007554105597
