MAMMALIAN OLIGOPEPTIDE TRANSPORTERS - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 132

for facilitating the active oral absorption of peptide-based drugs has been focused on
the PepT1 isoform. Recent evidence has suggested that the presence of other peptide
transporters, PHT isoforms and PT1, may require greater consideration. Assessing
and delineating the functional relevancy and overlap of these isoforms are needed to
properly understand their impact on peptide uptake and absorption.
Although attention to proper assessment of the functional relevancy of other
oligopeptides transporters is merited, there are several universal considerations that
will also hold true in all cases. The most important consideration is the impact of diet
on the function and expression of the transporters, which has been studied with PepT1
and to a lesser extent with PepT2. Hormonal regulation is another key element that
may be altered in certain disease states, in particular metabolic syndrome, which could
significantly alter the membrane expression and the clinical impact of oligopeptides
transporters. Further studies on the functional relevancy of the oligopeptide trans-
porter splice variants and SNPs are also warranted, especially when one considers the
two PepT1 splice variants that do convey functional relevancy. Many other factors
do exist, including the fact that we are still discovering new oligopeptides trans-
porter isoforms which will require significant efforts for their proper elucidation.
In short, it is apparent that considerably more research is required to character-
ize all of the functional peptide transporter systems to recognize their full clinical
impact.
Acknowledgments
The authors would like to acknowledge support provided by the National Institute
of General Medical Sciences (NIGMS; RO1-GM65448), the College of Pharmacy,
Nursing and Health Sciences, and the Department of Industrial and Physical Pharmacy
at Purdue University.
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