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Alcohol Clin Exp Res
2008 May 01;325:777-84. doi: 10.1111/j.1530-0277.2008.00636.x.
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Ethanol inhibits functional activity of the human intestinal dipeptide transporter hPepT1 expressed in Xenopus oocytes.
Li K
,
Xu L
,
Kulkarni AA
,
Perkins DI
,
Haworth IS
,
Davies DL
.
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The pathological effects of high alcohol (ethanol) consumption on gastrointestinal and hepatic systems are well recognized. However, the effects of ethanol intake on gastric and intestinal absorption and transport systems remain unclear. The present study investigates the effects of ethanol on the human peptide transporter 1 (hPepT1) which mediates the transport of di-and tripeptides as well as several orally administered peptidomimetic drugs such as beta-lactam antibiotics (e.g., penicillin), angiotensin-converting enzyme inhibitors, the anti-neoplastic agent bestatin, and prodrugs of acyclovir. Xenopus oocytes were injected with hPepT1 cRNA and incubated for 3 to 10 days. Currents induced by glycyl-sarcosine (Gly-Sar), Ala-Ala (dipeptides), penicillin and enalapril measured in the presence or absence of ethanol were determined using an 8-channel 2-electrode voltage clamp system, with a membrane potential of -70 mV and 11 voltage steps of 100 milliseconds (from +50 mV to -150 mV in -20 mV increments). Ethanol (200 mM) inhibited Gly-Sar and Ala-Ala currents by 42 and 30%, respectively, with IC(50)s of 184 and 371 mM, respectively. Ethanol reduced maximal transport capacity (I(max)) of hPepT1 for Gly-Sar without affecting Gly-Sar binding affinity (K(0.5) and Hill coefficient). Penicillin- and enalapril-induced currents were significantly less than those induced by dipeptides and were not inhibited by ethanol. Ethanol significantly reduced transport of dipeptides via a reduction in transport capacity, rather than competing for binding sites in hPepT1. Ethanol inhibition or alteration of transport function may be a primary causative factor contributing to both the nutritional deficits as well as the immunological deficiencies that many alcoholics experience including alcohol liver disease and brain damage.
Abramson,
Structure and mechanism of the lactose permease of Escherichia coli.
2003, Pubmed
Abramson,
Structure and mechanism of the lactose permease of Escherichia coli.
2003,
Pubmed
Adibi,
Regulation of expression of the intestinal oligopeptide transporter (Pept-1) in health and disease.
2003,
Pubmed
Ashida,
Thyroid hormone regulates the activity and expression of the peptide transporter PEPT1 in Caco-2 cells.
2002,
Pubmed
Balimane,
Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir.
1998,
Pubmed
,
Xenbase
Bockman,
Localization of peptide transporter in nuclei and lysosomes of the pancreas.
1997,
Pubmed
Bode,
Effect of alcohol consumption on the gut.
2003,
Pubmed
Brandsch,
Expression and protein kinase C-dependent regulation of peptide/H+ co-transport system in the Caco-2 human colon carcinoma cell line.
1994,
Pubmed
Davies,
Ethanol differentially affects ATP-gated P2X(3) and P2X(4) receptor subtypes expressed in Xenopus oocytes.
2005,
Pubmed
,
Xenbase
Dean,
The human ATP-binding cassette (ABC) transporter superfamily.
2001,
Pubmed
Erickson,
Regional expression and dietary regulation of rat small intestinal peptide and amino acid transporter mRNAs.
1995,
Pubmed
Fei,
Expression cloning of a mammalian proton-coupled oligopeptide transporter.
1994,
Pubmed
,
Xenbase
Ganapathy,
Proton-coupled solute transport in the animal cell plasma membrane.
1991,
Pubmed
Ganapathy,
Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2.
1998,
Pubmed
Gutjahr,
Relation between average alcohol consumption and disease: an overview.
2001,
Pubmed
Halsted,
Nutrition and alcoholic liver disease.
2004,
Pubmed
Hediger,
The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteinsIntroduction.
2004,
Pubmed
Irie,
Computational modelling of H+-coupled peptide transport via human PEPT1.
2005,
Pubmed
Israel,
Alcohol and amino acid transport in the human small intestine.
1969,
Pubmed
Kulkarni,
A charge pair interaction between Arg282 in transmembrane segment 7 and Asp341 in transmembrane segment 8 of hPepT1.
2007,
Pubmed
Kulkarni,
Transmembrane segment 5 of the dipeptide transporter hPepT1 forms a part of the substrate translocation pathway.
2003,
Pubmed
,
Xenbase
Kulkarni,
Analysis of transmembrane segment 7 of the dipeptide transporter hPepT1 by cysteine-scanning mutagenesis.
2003,
Pubmed
Lee,
Membrane transporters.
2000,
Pubmed
Liang,
Human intestinal H+/peptide cotransporter. Cloning, functional expression, and chromosomal localization.
1995,
Pubmed
,
Xenbase
Mackenzie,
Mechanisms of the human intestinal H+-coupled oligopeptide transporter hPEPT1.
1996,
Pubmed
,
Xenbase
Meredith,
Oligopeptide transport by epithelial cells.
1995,
Pubmed
Muller,
Inhibition of the H+/peptide cotransporter in the human intestinal cell line Caco-2 by cyclic AMP.
1996,
Pubmed
Nielsen,
Epidermal growth factor inhibits glycylsarcosine transport and hPepT1 expression in a human intestinal cell line.
2001,
Pubmed
Poschet,
Characterisation of penicillin G uptake in human small intestinal brush border membrane vesicles.
1999,
Pubmed
Preedy,
Gastrointestinal protein turnover and alcohol misuse.
1993,
Pubmed
Rajendram,
Effect of alcohol consumption on the gut.
2005,
Pubmed
Rehm,
The global distribution of average volume of alcohol consumption and patterns of drinking.
2003,
Pubmed
Sala-Rabanal,
Molecular interactions between dipeptides, drugs and the human intestinal H+ -oligopeptide cotransporter hPEPT1.
2006,
Pubmed
,
Xenbase
Shiraga,
Cellular and molecular mechanisms of dietary regulation on rat intestinal H+/Peptide transporter PepT1.
1999,
Pubmed
Siegmund,
Animal models and their results in gastrointestinal alcohol research.
2005,
Pubmed
Sun,
Changes of biological functions of dipeptide transporter (PepT1) and hormonal regulation in severe scald rats.
2003,
Pubmed
Sundaram,
Mechanism of inhibition of proton: dipeptide co-transport during chronic enteritis in the mammalian small intestine.
2005,
Pubmed
Tamai,
The predominant contribution of oligopeptide transporter PepT1 to intestinal absorption of beta-lactam antibiotics in the rat small intestine.
1997,
Pubmed
,
Xenbase
Tamai,
Improvement of L-dopa absorption by dipeptidyl derivation, utilizing peptide transporter PepT1.
1998,
Pubmed
,
Xenbase
Terada,
Expression profiles of various transporters for oligopeptides, amino acids and organic ions along the human digestive tract.
2005,
Pubmed
Thamotharan,
An active mechanism for completion of the final stage of protein degradation in the liver, lysosomal transport of dipeptides.
1997,
Pubmed
Thamotharan,
Hormonal regulation of oligopeptide transporter pept-1 in a human intestinal cell line.
1999,
Pubmed
Zhu,
Differential recognition of ACE inhibitors in Xenopus laevis oocytes expressing rat PEPT1 and PEPT2.
2000,
Pubmed
,
Xenbase
Ziegler,
Distribution of the H+/peptide transporter PepT1 in human intestine: up-regulated expression in the colonic mucosa of patients with short-bowel syndrome.
2002,
Pubmed