The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology.
Level 5 - mechanism / opinion, no new human data
Narrative review of transporter physiology and pharmacology with mechanism-based reasoning and no new human data.
PubMed 12905028 · doi:10.1007/s00424-003-1101-4
What was done
This narrative review synthesizes structural, functional, and pharmacological findings regarding the mammalian SLC15 proton-dependent oligopeptide cotransporter family, specifically PEPT1 (SLC15A1), PEPT2 (SLC15A2), PHT1 (SLC15A4), and PHT2 (SLC15A3).
What was found
The abstract reports no numerical data. It notes that PEPT1 and PEPT2 electrogenically transport essentially all di- and tripeptides regardless of charge in a stereoselective manner, along with peptidomimetic drugs. PEPT1 operates in intestinal and bile duct epithelia; PEPT2 is found in renal tubules, glial cells, choroid plexus, lung, and mammary gland. PHT1 and PHT2 share 20% to 25% sequence identity with PEPT proteins and transport free histidine and certain peptides, with uncertain localization between plasma and lysosomal membranes.
Why it matters
PEPT1 and PEPT2 govern the intestinal absorption and renal reabsorption of peptidomimetic therapeutics, making them central targets for prodrug design and pharmacokinetic optimization.
Limits
As a narrative review, no primary quantitative measurements, sample sizes, or clinical trial data are presented in the abstract. Subcellular localization and in vivo physiological roles of PHT1 and PHT2 remained unconfirmed.
Cited by
- supports Di- and tripeptides can be orally bioavailable if they have the appropriate conformation and size.