Substrates of the human oligopeptide transporter hPEPT2

Zhao, Dongxin; Lü, Kui

doi:10.5582/bst.2015.01078

Cited by 18 publications

(12 citation statements)

References 63 publications

(61 reference statements)

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“…More importantly, it inhibits the human peptide transporter, hPepT2 [ 247 ], which is expressed in astrocytes, subependymal cells, ependymal cells and epithelial cells of the choroid plexus [ 248 ]. hPepT2 is responsible for clearing di- and tripeptides, ACE inhibitors, and other substances from the cerebrospinal fluid [ 249 , 250 ]. Thus, Val–Pro may prevent the clearance of other venom hypotensive peptides, further deepening the hypotension induced by other venom constituents.…”

Section: Resultsmentioning

confidence: 99%

Organic and Peptidyl Constituents of Snake Venoms: The Picture Is Vastly More Complex Than We Imagined

Villar‐Briones

Aird

2018

Toxins

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Small metabolites and peptides in 17 snake venoms (Elapidae, Viperinae, and Crotalinae), were quantified using liquid chromatography-mass spectrometry. Each venom contains >900 metabolites and peptides. Many small organic compounds are present at levels that are probably significant in prey envenomation, given that their known pharmacologies are consistent with snake envenomation strategies. Metabolites included purine nucleosides and their bases, neurotransmitters, neuromodulators, guanidino compounds, carboxylic acids, amines, mono- and disaccharides, and amino acids. Peptides of 2–15 amino acids are also present in significant quantities, particularly in crotaline and viperine venoms. Some constituents are specific to individual taxa, while others are broadly distributed. Some of the latter appear to support high anabolic activity in the gland, rather than having toxic functions. Overall, the most abundant organic metabolite was citric acid, owing to its predominance in viperine and crotaline venoms, where it chelates divalent cations to prevent venom degradation by venom metalloproteases and damage to glandular tissue by phospholipases. However, in terms of their concentrations in individual venoms, adenosine, adenine, were most abundant, owing to their high titers in Dendroaspis polylepis venom, although hypoxanthine, guanosine, inosine, and guanine all numbered among the 50 most abundant organic constituents. A purine not previously reported in venoms, ethyl adenosine carboxylate, was discovered in D. polylepis venom, where it probably contributes to the profound hypotension caused by this venom. Acetylcholine was present in significant quantities only in this highly excitotoxic venom, while 4-guanidinobutyric acid and 5-guanidino-2-oxopentanoic acid were present in all venoms.

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Section: Resultsmentioning

confidence: 99%

Organic and Peptidyl Constituents of Snake Venoms: The Picture Is Vastly More Complex Than We Imagined

Villar‐Briones

Aird

2018

Toxins

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“…A unique feature of this group of transporters is the diversity of substrates because substrate affinity is unaffected by peptide charge ( 31 , 32 ). To evaluate peptide transport in our experiments, we used the first-generation cephalosporin antibiotic cefadroxil as a competitive inhibitor of PEPT2 transporter.…”

Section: Discussionmentioning

confidence: 99%

A mechanism for matrikine regulation in acute inflammatory lung injury

Robison

Viera

et al. 2021

JCI Insight

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“…Lastly, a significant decrease in the renal expression of Pept2 was observed in PbA‐infected mice receiving regular water. PEPT2 is the predominant transporter involved in the renal absorption of di‐ and tripeptides as well as β‐lactam antibiotics and angiotensin‐converting enzyme (ACE) inhibitors . Thus, infection may impact their renal drug clearance.…”

Section: Discussionmentioning

confidence: 99%

“…PEPT2 is the predominant transporter involved in the renal absorption of di-and tripeptides as well as β-lactam antibiotics and angiotensin-converting enzyme (ACE) inhibitors. 50 Thus, infection may impact their renal drug clearance.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of solute carrier transporters in malaria‐infected pregnant mice

Najjar

McColl

Weckman

et al. 2019

Parasite Immunology

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Summary Aims Malaria in pregnancy (MiP) alters the expression of ATP‐binding cassette efflux transporters in maternal and foetal tissues, as well as the placenta. Malaria induces oxidative stress, and pregnancy is associated with arginine deficiency. We hypothesized that reducing oxidative stress during MiP by supplementation with L‐arginine, a NO precursor, would attenuate transcriptional changes in a second superfamily of transporters, solute carrier (SLC) transporters, and improve pregnancy outcomes. Methods and Results Pregnant BALB/c mice receiving L‐arginine (1.2%) in water, or water alone, were infected with Plasmodium berghei ANKA on gestational day 13 and sacrificed on gestational day 19. Compared to controls, the mRNA of numerous SLC transporters was downregulated in maternal and foetal tissues, as well as in the placentas of infected mice. While supplementation with L‐arginine did improve foetal viability, it did not improve the mRNA expression of oxidative stress markers, transporters nor other indices of foetal and maternal health. Moreover, amino acid uptake transporters were downregulated upon infection, which could potentially contribute to decreased foetal birthweight. Conclusions Malaria in pregnancy significantly alters the expression of SLC transporters in maternal and foetal tissues as well as the placenta, regardless of L‐arginine supplementation. Further studies to investigate methods of reducing oxidative stress in MiP are warranted.

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Substrates of the human oligopeptide transporter hPEPT2

Cited by 18 publications

References 63 publications

Organic and Peptidyl Constituents of Snake Venoms: The Picture Is Vastly More Complex Than We Imagined

Organic and Peptidyl Constituents of Snake Venoms: The Picture Is Vastly More Complex Than We Imagined

A mechanism for matrikine regulation in acute inflammatory lung injury

Dysregulation of solute carrier transporters in malaria‐infected pregnant mice

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