The oligopeptide transporter (Pept-1) in human intestine: Biology and function

Adibi, Siamak A.

doi:10.1016/s0016-5085(97)70112-4

Cited by 308 publications

(207 citation statements)

References 4 publications

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“…The transport of substrate via hPEPT1 is unequivocally driven by an inward H ϩ electrochemical potential gradient. 2,3,12) As to the bell-shaped activity of hPEPT1 vs. pH, the reason why the transport activity decreases with an increase in pH is obviously due to the decrease in the driving force of the proton electrochemical gradient. On the other hand, based on the driving force of hPEPT1, the uptake activity would increase when extracellular pH decreases.…”

Section: Discussionmentioning

confidence: 99%

“…2,3,12) It has been demonstrated in intestinal membrane vesicles, 4,13,14) Xenopus oocytes 15) and culture cells 16) that the transport activity of PEPT1 shows a bellshaped pH dependence with an optimal pH 5.5 to 6.0. This optimal pH is physiologically collaborated with an acidic unstirred water layer (pH 5.5-6.0) in the intestinal lumen.…”

Section: )mentioning

confidence: 99%

“…The uptake data in the presence of nigericin/monensin were fitted to the Henderson-Hasselbalch equation as follows, (2) where u represents the initial rate of Gly-Sar transport; V max,o , the maximum value of transport rate; pH, the medium pH; pKa, the association of the proton, respectively. …”

Section: Construction Of Expression Vector Pcineo/hpept1mentioning

confidence: 99%

“…1) Therefore, a majority of protein digestion products are obligatorily absorbed via an intestine oligo-peptide transporter called PEPT1. Of interest, PEPT1 also mediates the absorption of a huge number of pharmacologically important compounds including peptidomimetic drugs, 2,3) such as oral b-lactam antibiotics, [4][5][6] ACE-inhibitors like captopril, 7) or the peptidase inhibitor bestatine 8) and even compounds without an obvious peptide bond or equivalent, 9) such as d-amino levulinic acid. 10) This surprisingly high tolerance for structural diversity of the substrate by PEPT1 has been expected to be used as a channel to increase the intestinal absorption of poorly absorbable drugs.…”

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confidence: 99%

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The Extracellular pH Dependency of Transport Activity by Human Oligopeptide Transporter 1 (hPEPT1) Expressed Stably in Chinese Hamster Ovary (CHO) Cells: A Reason for the Bell-Shaped Activity versus pH

Fujisawa

Tateoka

Nara

et al. 2006

Biological & Pharmaceutical Bulletin

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It has been estimated that more than 80% of amino acids found in the intestinal lumen after a protein meal are in the form of small peptides rather than free amino acids.1) Therefore, a majority of protein digestion products are obligatorily absorbed via an intestine oligo-peptide transporter called PEPT1. Of interest, PEPT1 also mediates the absorption of a huge number of pharmacologically important compounds including peptidomimetic drugs, 2,3) such as oral b-lactam antibiotics, 4-6) ACE-inhibitors like captopril, 7) or the peptidase inhibitor bestatine 8) and even compounds without an obvious peptide bond or equivalent, 9) such as d-amino levulinic acid.10) This surprisingly high tolerance for structural diversity of the substrate by PEPT1 has been expected to be used as a channel to increase the intestinal absorption of poorly absorbable drugs. 11)The transport of substrates via PEPT1 is coupled to the downward movement of a proton in accordance with its electrochemical gradient. 2,3,12) It has been demonstrated in intestinal membrane vesicles, 4,13,14) Xenopus oocytes 15) and culture cells 16) that the transport activity of PEPT1 shows a bellshaped pH dependence with an optimal pH 5.5 to 6.0. This optimal pH is physiologically collaborated with an acidic unstirred water layer (pH 5.5-6.0) in the intestinal lumen. 1,17) Hence, PEPT1 can function most efficiently in epithelial cells of the small intestine.As for the bell-shaped activity of PEPT1 vs. pH, the reason why the transport activity decreases with an increase in pH is obviously the decrease in the driving force of the proton electrochemical potential gradient. On the other hand, why does the activity decrease in a more acidic region although the driving force should increase? To answer this question, we will try to obtain a relationship between the transport activity and extracellular pH. However, there is a problem to be solved: The driving force changes along with the change in extracellular pH. The pH-dependent properties of PEPT1 should be determined without changing the driving force. Here, we employ the experimental condition that the proton concentration gradient across the membrane is dissipated by the addition of monensin and nigericin 18,19) ; then the driving force is solely the membrane potential. To perform this experiment, a cell line is necessary which shows high transport activity. First, we established stably transfected CHO cells which show high transport activities for various substrates with almost the same K m values as those obtained from those of a model human intestine epithelial cell line, Caco-2. [20][21][22] Thus, this CHO cell line over-expressing hPEPT1 (designated as CHO/hPEPT1) is useful and convenient for transport studies of hPEPT1. In the present study, we then examined the pH-dependency of transport activity by hPEPT1 using CHO/hPEPT1 cells. Human oligopeptide transporter (hPEPT1) translocates di/tri-peptide by coupling to movement of proton down the electrochemical gradient. This transporter has the characteristics ...

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Section: Discussionmentioning

confidence: 99%

Section: )mentioning

confidence: 99%

Section: Construction Of Expression Vector Pcineo/hpept1mentioning

confidence: 99%

mentioning

confidence: 99%

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The Extracellular pH Dependency of Transport Activity by Human Oligopeptide Transporter 1 (hPEPT1) Expressed Stably in Chinese Hamster Ovary (CHO) Cells: A Reason for the Bell-Shaped Activity versus pH

Fujisawa

Tateoka

Nara

et al. 2006

Biological & Pharmaceutical Bulletin

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“…Approximately 70% of digested proteins are absorbed as small peptides composed of two (dipeptides) or three (tripeptides) amino acids, whereas the remaining 30% are absorbed as a single amino acid (1,2). Although single amino acids are taken up into enterocytes through numerous amino acid transporters, the intestinal absorption of di-and tripeptides are mediated via only one transport system consisting of PepT1 2 (3,4). PepT1 is encoded by soluble carrier protein family 15 member 1 (Slc15a1) and mainly expressed in the apical plasma membrane in intestinal epithelial cells (5,6).…”

mentioning

confidence: 99%

Bile Acid-regulated Peroxisome Proliferator-activated Receptor-α (PPARα) Activity Underlies Circadian Expression of Intestinal Peptide Absorption Transporter PepT1/Slc15a1

Okamura

Koyanagi

Dilxiat

et al. 2014

Journal of Biological Chemistry

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Background: Intestinal expression of peptide absorption transporter (PepT1)/Slc15a1 exhibits circadian oscillation, but the mechanism is unknown. Results: During the daily feeding cycle, bile acids accumulated in intestinal cells, thereby suppressing PPAR␣-mediated expression of PepT1/Slc15a1. Conclusion: Time-dependent suppression of PPAR␣ activity by bile acids underlies circadian expression of PepT1/Slc15a1. Significance: Bile acids cause circadian change in the intestinal absorption of peptides.

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Membrane Transport Proteins and Drug Transport

Swaan

2003

Burger's Medicinal Chemistry and Drug Discovery

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To exert their intended therapeutic goal, drugs need to cross epithelial barriers to reach their site of action. Transport proteins have critical physiological roles in nutrient absorption and transport of endogenous compounds. These systems can serve as useful pharmacological targets and may be used as a mechanism to increase drug absorption. However, we have little understanding of these proteins at the molecular level because of the absence of high resolution crystal structures. Numerous efforts have been made to characterize the P‐glycoprotein efflux pump, the peptide transporter PepT1, and the apical sodium‐dependent transporter, which are important not only for their native transporter function but also as drug targets to increase absorption and bioactivity. In vitro and computational approaches have been applied to gain some insight into these transporters with some success. This represents an opportunity for optimizing molecules as substrates for the solute transporters and providing a further screening system for drug discovery. Clearly the future growth in knowledge of transporter function will be led by integrated in vitro and in silico approaches.

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The oligopeptide transporter (Pept-1) in human intestine: Biology and function

Cited by 308 publications

References 4 publications

The Extracellular pH Dependency of Transport Activity by Human Oligopeptide Transporter 1 (hPEPT1) Expressed Stably in Chinese Hamster Ovary (CHO) Cells: A Reason for the Bell-Shaped Activity versus pH

The Extracellular pH Dependency of Transport Activity by Human Oligopeptide Transporter 1 (hPEPT1) Expressed Stably in Chinese Hamster Ovary (CHO) Cells: A Reason for the Bell-Shaped Activity versus pH

Bile Acid-regulated Peroxisome Proliferator-activated Receptor-α (PPARα) Activity Underlies Circadian Expression of Intestinal Peptide Absorption Transporter PepT1/Slc15a1

Membrane Transport Proteins and Drug Transport

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