Distribution of peptide transporter PEPT2 mRNA in the rat nervous system

Berger, Urs V.; Hediger, Matthias A.

doi:10.1007/s004290050242

Cited by 130 publications

(92 citation statements)

References 26 publications

(20 reference statements)

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“…Another high affinity peptide transporter, PEPT2, has been shown to be present in the central nervous system by Northern blot and in situ hybridization studies in mammals (9,14,15). The ectopic expression approach proves to be particularly useful for pinpointing the precise time and place of GFP expression because cell lineages can be simultaneously observed using differential interference contrast imaging.…”

Section: Discussionmentioning

confidence: 99%

“…These studies suggest that OPT3 might play an important role in H ϩ homeostasis in C. elegans in addition to its likely role in the clearance of peptides arising from neuropeptide metabolism. In mammals, PEPT2 is expressed in the brain, and a similar role for this transporter in the clearance of peptide products arising from the hydrolysis of neuropeptides within the brain has been postulated (13)(14)(15)(16).…”

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confidence: 96%

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A Novel H+-coupled Oligopeptide Transporter (OPT3) from Caenorhabditis elegans with a Predominant Function as a H+ Channel and an Exclusive Expression in Neurons

Fei¹,

Romero²,

Krause³

et al. 2000

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

A Novel H+-coupled Oligopeptide Transporter (OPT3) from Caenorhabditis elegans with a Predominant Function as a H+ Channel and an Exclusive Expression in Neurons

Fei¹,

Romero²,

Krause³

et al. 2000

Journal of Biological Chemistry

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“…More recently, PEPT2 has been identified in the peripheral nervous system, in the membranes and cytoplasm of satellite glial cells surrounding the ganglionic neurons (29), and in the central nervous system. In situ hybridization analysis revealed its presence in the brain in astrocytes, ependymal and subependymal cells, and in epithelial cells of the choroid plexus (8). In the lung, PEPT2 is expressed in type II pneumocytes and in the apical membrane of tracheal and bronchial epithelial cells (31).…”

Section: Tissue Distribution Of Pept1 and Pept2 And Their Tubular Locmentioning

confidence: 99%

An update on renal peptide transporters

Daniel

Rubio‐Aliaga

2003

American Journal of Physiology-Renal Physiology

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Daniel, Hannelore, and Isabel Rubio-Aliaga. An update on renal peptide transporters. Am J Physiol Renal Physiol 284: F885-F892, 2003; 10.1152/ajprenal.00123.2002The brush-border membrane of renal epithelial cells contains PEPT1 and PEPT2 proteins that are rheogenic carriers for short-chain peptides. The carrier proteins display a distinct surface expression pattern along the proximal tubule, suggesting that initially di-and tripeptides, either filtered or released by surface-bound hydrolases from larger oligopeptides, are taken up by the low-affinity but high-capacity PEPT1 transporter and then by PEPT2, which possesses a higher affinity but lower transport capacity. Both carriers transport essentially all possible di-and tripeptides and numerous structurally related drugs. A unique feature of the mammalian peptide transporters is the capability of proton-dependent electrogenic cotransport of all substrates, regardless of their charge, that is achieved by variable coupling in proton movement along with the substrate down the transmembrane potential difference. This review focuses on the postcloning research efforts to understand the molecular physiology of peptide transport processes in renal tubules and summarizes available data on the underlying genes, protein structures, and transporter function as derived from studies in heterologous expression systems. PEPT1; PEPT2; renal physiology; localization; functional analysis RENAL TUBULAR PEPTIDE TRANSPORT activity was originally discovered after intravenous infusion of the resistant dipeptide Gly-Sar in rats that resulted in a high accumulation of the intact dipeptide in renal tissue (1, 3). Studies with renal brush-border membrane vesicles established that renal apical peptide uptake was an electrogenic, proton-dependent uphill transport process for di-and tripeptides and related drugs mediated by two kinetically different systems (for a review, see Ref. 38). The underlying proteins, differing in transport characteristics, now designated as PEPT1 (SLC15A1) and PEPT2 (SLC15A2), have been identified, and the corresponding genes have been cloned from a variety of species (10,24,25,39,41,(52)(53)(54). The transporters have been expressed in various cellular models, and information on structure, transport function, and regulation has been gathered by flux studies and electrophysiological techniques. Expression analysis of transporter mRNA and protein by in situ hybridization and immunohistochemistry has extended our knowledge of tissue distribution, particularly the renal zonation of PEPT1 and PEPT2 surface expression. THE MOLECULAR ENTITIES OF APICAL PEPTIDE TRANSPORTPEPT1 and PEPT2 are polytopic integral membrane proteins with 12 predicted membrane-spanning domains and NH 2 -and COOH-terminal ends facing the cytosol. Transporter architecture and membrane topology have not been studied systematically, and therefore structural information is still mainly based on hydropathic analysis of amino acid sequences. The mammalian PEPT1 proteins comprise 701-710 amino acids, ...

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“…It was initially cloned from a human kidney cDNA library (4) and is characterized as a high affinity (i.e., M K m values), low capacity transporter (5). PEPT2 mRNA transcripts (6,7), protein (8,9) and functional activity (10)(11)(12)(13)(14), along with PHT1 mRNA transcripts (15) have been described in the choroid plexus. Functional and immunocytochemical data in primary cultures of rat choroid plexus epithelial cells have demonstrated that PEPT2 is expressed on the apical plasma membrane (i.e., CSF-facing) and functions to clear di-and tripeptides from CSF (9).…”

Section: Introductionmentioning

confidence: 99%

Role of PEPT2 in the Choroid Plexus Uptake of Glycylsarcosine and 5-Aminolevulinic Acid: Studies in Wild-Type and Null Mice

Ocheltree

Shen

et al. 2004

Pharm Res

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Purpose. To determine the importance of PEPT2 in the uptake of glycylsarcosine (GlySar) and 5-aminolevulinic acid (5-ALA) in mouse choroid plexus whole tissue. Methods. Uptake studies were performed in bicarbonate artificial cerebrospinal fluid buffer using choroid plexuses isolated from PEPT2 +/+ and PEPT2 −/− mice. Results. PEPT2−/− mice exhibited a 90% reduction in GlySar uptake (p < 0.001) and a 92% reduction in 5-ALA uptake (p < 0.001) as compared to wild type animals. At 4°C (vs. 37°C), GlySar uptake was reduced by 95% in PEPT2 +/+ mice; no difference was observed in null animals. Unlabeled GlySar inhibited the uptake of [ ). Low sodium buffer (1 mM) resulted in 75% and 59% reductions, respectively, in GlySar (p < 0.001) and 5-ALA (p < 0.01) uptake in PEPT2 +/+ mice; no differences were observed in PEPT2 −/− mice. Overall, about 90-95% of the choroid plexus uptake of GlySar and 5-ALA was mediated by PEPT2, with about 5-10% of the residual uptake occurring by nonspecific mechanisms.Conclusions. The results demonstrate that PEPT2 is the only transporter responsible for the choroid plexus uptake of GlySar and 5-ALA. They also suggest a role for PEPT2 in the clearance of dipeptides and endogenous peptidomimetics from cerebrospinal fluid.

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Distribution of peptide transporter PEPT2 mRNA in the rat nervous system

Cited by 130 publications

References 26 publications

A Novel H+-coupled Oligopeptide Transporter (OPT3) from Caenorhabditis elegans with a Predominant Function as a H+ Channel and an Exclusive Expression in Neurons

A Novel H+-coupled Oligopeptide Transporter (OPT3) from Caenorhabditis elegans with a Predominant Function as a H+ Channel and an Exclusive Expression in Neurons

An update on renal peptide transporters

Role of PEPT2 in the Choroid Plexus Uptake of Glycylsarcosine and 5-Aminolevulinic Acid: Studies in Wild-Type and Null Mice

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