Abstract
Peptide transporter-1 is a H+/peptide cotransporter responsible for the uptake of small peptides and peptide-like drugs, and is present in the absorptive epithelial cells of the villi in the small intestine (duodenum, jejunum, and ileum). It has been localized to the apical microvillous plasma membrane of the absorptive epithelial cells of the rat small intestine using the immunogold electron microscopic technique. Digital image analysis of the jejunum revealed that the transporter protein was abundant at the tip of the villus and that the amount decreased from the tip of the villus to its base. The effect of dietary administration of amino acids and starvation on the expression of PepT1 in the jejunum was examined by immunoblotting and image analysis of immunofluorescence. Starvation markedly increased the amount of peptide transporter present, whereas dietary administration of amino acids reduced it. The gradient of the transporter protein along the crypt-villus axis was maintained under either condition. These observations show that it is specific to the microvillous plasma membrane and that its expression is regulated by the nutritional condition.
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References cited
Adibi SA (1997) The oligopeptide transporter (Pept-1) in human intestine: biology function. Gastroenterol 113: 332-340.
Boll M, Markovich D, Weber WM, Korte H, Daniel H, Murer H (1994) Expression cloning of a cDNA from rabbit small intestine related to proton-coupled transport peptides, beta-lactam antibiotics and ACEinhibitors. Pflügers Arch Eur J Physiol 429: 146-149.
Boll M, Herget M, Wagerner M, Weber WM, Maricovich D, Biber J, Clauss W, Murer H, Daniel H(1996) Expression cloning and functional characterization of the kidney cortex high-affinity proton-coupled peptide transporter. Proc Natl Acad Sci USA 93: 284-289.
H, Leblond CP (1974) Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. Am J Anat 141: 461-480.
RH, Gum JR Jr, Lindstrom MM, McKean D, Kim YS (1995) Regional expression and dietary regulation of rat small intestinal peptide and amino acid transporter mRNAs. Biochem Biophys Res Commun 216: 249-257.
Fei YJ, Kanai Y, Nussberger S, Ganapathy V, Leibach FH, Romero MF, Singh SK, Boron WF, Hediger MA (1994) Expression cloning of a mammalian proton-coupled oligopeptide transporter. Nature 368: 563-566.
Ferraris RP, Diamond J, Kwan WW (1988a) Dietary regulation of intestinal transport of the dipeptide carnosine. Am J Physiol 255: G143-G150.
Ferraris RP, Kwan WW, Diamond J (1988b) Regulatory signals for intestinal amino acid transporters and peptidases. Am J Physiol 255: G151-G157.
Freeman TC, Bentsen BS, Thwaites DT, Simons NL (1995) HC/Dipeptide transporter(PepT1) expression in the rabbit intestine. Fflügers Arch Eur J Physiol 430: 394-400.
Ganapathy ME, Brandsh M, Prasad PD, Ganapathy V, Leibach FH (1995) Differential recognition of β-lactam antibiotics by intestinal and renal peptide transporters, PepT1 and PepT2. J Biol Chem 270: 25672-25677.
Ganapathy V, Leibach FH (1985) Is intestinal peptide transport energized by a proton gradient? Am J Physiol 249: G153-G160.
Higuchi K, Shimizu Y, Nambu S, Miyabayashi C, Takahara T, Saito S, Hioki O, Kuwabara Y, Watanabe A (1994) Effects of an infusion of branched-chain amino acids on neurophysiological and psychometric testings in chirrhotic patients with mild hepatic encephalopathy. J Gastroenterol Hepatol 9: 366-372.
Hwang ES, Hirayama BA, Wright EM (1991) Distribution of the SGLT1 Na+/glucose cotransporter and mRNA along the crypt-villi axis of rabbit small intestine. Biochem Biophys Res Commun 181: 1208-1217.
Leibach FH, Ganapathy V (1996) Peptide transporters in the rat intestine and kidney. Annu Rev Nutr 16: 99-119.
Liang R, Fei YJ, Prasad PD, Ramamoorthy S, Han H, Yang-Feng TL, Hediger MA, Ganapathy V, Leibach FH (1995) Human intestinal H+/peptide cotransporter: cloning, functional expression, and chromosomal localization. J Biol Chem 270: 6456-6463.
Liu W, Liang R, Ramamoorthy S, Fei YJ, Ganapathy ME, Hediger MA, Ganapathy V, Leibach FH (1995) Molecular cloning of PEPT2, a new member of the H+/peptide cotransporter family from human kidney. Biochim Biophys Acta 1235: 461-466.
Mailliard ME, Stevens BR, Mann GE (1995) Amino acid transport by small intestinal hepatic and pancreatic epithelia. Gastroenterology 108: 888-910.
Malandro MS, Kilberg MS (1996) Molecular biology of mammalian amino acid transporters. Annu Rev Biochem 65: 305-336.
Marway JS, Bateman CJ, Preedy VR (1993) The extraction of smooth muscle contractile and noncontractile proteins from the rat small intestine: measurement of protein synthesis and effects of ethanol toxicity. Anal Biochem 209: 95-103.
McGivan JD, Pastor-Anglada M (1994) Regulatory and molecular aspects of mammalian amino acid transport. Biochem J 299: 321-334.
Miyamoto K, Hase K, Takagi T, Fujii T, Taketani Y, Minami H, Oka T, Nakabou Y (1993) Differential responses of intestinal glucose transporter mRNA transcripts to levels of dietary sugars. Biochem J 295: 211-215.
Ogihara H, Saito H, Shin B-C, Terada T, Takenoshita S, Nagamachi Y, Inui K, Takata K (1996) Immuno-localization of H+/peptide cotransporter in rat digestive tract. Biochem Biophys Res Commun 220: 848-852.
Ramamoorthy S, Liu W, Ma YY, Yang-Feng TL, Ganapathy V, Leibach FH (1995) Proton/peptide cotransporter (PEPT 2) from human kidney: functional characterization and chromosomal localization. Biochym Biophys Acta 1240: 1-4.
Saito H, Okuda M, Terada T, Sasaki S, Inui K (1995) Cloning and characterization of a rat H+/peptide cotransporter mediating absorption of beta-lactam antibiotics in the intestine and kidney. J Pharmacol Exp Ther 275: 1631-1637.
Saito H, Terada T, Okuda M, Sasaki S, Inui K (1996) Molecular cloning and tissue distribution of rat peptide transporter PEPT2. Biochim Biophys Acta 1280: 173-177.
Sawada H, Esaki M (1994) Use of nanogold followed by silver enhancement and gold toning for pre-embedding immunolocalization in osmium-fixed, epon-embedded tissues. J Electron Microsc 43: 361-366.
Shin B-C, Suzuki T, Matsuzaki T, Tanaka S, Kuraoka A, Shibata Y, Takata K (1996) Immunolocalization of GLUT1 and connexin 26 in the rat placenta. Cell Tissue Res 285: 83-89.
Shirazi-Beechey SP, Hirayama BA, Wang Y, Scott D, Smith MW, Wright EM (1991) Ontogenic development of lamb intestinal sodiumglucose co-transporter is regulated by diet. J Physiol 437: 699-708.
Takata K, Kasahara T, Kasahara M, Ezaki O, Hirano H (1992) Immunohistochemical localization of Na+-dependent glucose transporter in rat jejunum. Cell Tissue Res 267: 3-9.
Terada T, Saito H, Mukai M, Inui K (1997a) Characterization of stably transfected kidney epithelial cell line expressing rat H+/peptide cotransporter PepT1: localization of PepT1 and transport of β-lactam antibiotics. J Pharmacol Exp Ther 281: 1415-1421.
Terada T, Saito H, Mukai M, Inui K (1997b) Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am J Physiol 273: F706-F711.
Thorens B, Cheng ZQ, Brown D, Lodish HF (1990) Liver glucose transporter: a basolateral protein in hepatocytes and intestine and kidney cells. Am J Physiol 259: C279-C285.
Tomita Y, Takano M, Yasuhara M, Hori R, Inui K (1995) Transport of oral cephalosporins by the H+/dipeptide cotransporter and distribution of the transport activity in isolated rabbit intestinal epithelial cells. J Pharmacol Exp Ther 272: 63-69.
Wenzel U, Thwaites DT, Daniel H (1995) Stereoselective uptake of β-lactam anibiotics by the intestinal peptide transporter. British J Pharmacol 116: 3021-3027.
Yoshida A, Takata K, Kasahara T, Aoyagi T, Saito S, Hirano H (1995) Immunohistochemical localization of Na+-dependent glucose transporter in the rat digestive tract. Histochem J 27: 420-426.
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Ogihara, H., Suzuki, T., Nagamachi, Y. et al. Peptide Transporter in the Rat Small Intestine: Ultrastructural Localization and the Effect of Starvation and Administration of Amino Acids. Histochem J 31, 169–174 (1999). https://doi.org/10.1023/A:1003515413550
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DOI: https://doi.org/10.1023/A:1003515413550