{"title":"Functional and Physiological Implications of Oligopeptide Transporters: Potential Targets for Pharmacological Interventions.","authors":"Tapas Roy, Madhu Nath, Nabanita Halder, Rohit Saxena, Thirumurthy Velpandian","doi":"10.1007/s00232-025-00348-1","DOIUrl":null,"url":null,"abstract":"<p><p>Peptide transporters are important plasma membrane proteins that facilitate the cellular uptake of di- and tripeptides in addition to various peptidomimetic drugs. The proton-coupled oligopeptide transporter (POT) family consists of mainly four transporter proteins, which include two H<sup>+</sup> -coupled oligopeptide transporters known as PEPT1 (SLC15A1) and PEPT2 (SLC15A2), along with two peptide/histidine transporters referred to as PHT1 (SLC15A4) and PHT2 (SLC15A3). These transporters play an important role in the drug delivery process in mammalian tissues. They are highly expressed in tissues such as the small intestine, kidney, liver, lung, and eye. PHT1 shows expression in immune cells, especially in B cells and plasmacytoid dendritic cells. The pathophysiological relevance of peptide transporters is emerging to be crucial in various disease conditions, e.g., PEPT1 plays a role in the physiopathology of the gastrointestinal system, particularly in IBD. Upregulated expression of peptide transporters has also been positively related to inflammatory responses. An increasing number of peptide-based drug therapies have been reported to have the potential for development of novel classes of drugs. For example, Carnosine (beta-alanyl-L-histidine) has been demonstrated to act as an antioxidant, antiglycating agent, and neuroprotector. It is transported by PEPT1 and PEPT2, facilitating its protective effects against oxidative stress in neurons and intestinal epithelial cells. Moreover, it has applications in the treatment of multidrug-resistant cancers and has been shown to improve glucose metabolism. This review gives an insight into the functional, physiological and pharmacological importance of proton-coupled oligopeptide transporter.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Membrane Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s00232-025-00348-1","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Peptide transporters are important plasma membrane proteins that facilitate the cellular uptake of di- and tripeptides in addition to various peptidomimetic drugs. The proton-coupled oligopeptide transporter (POT) family consists of mainly four transporter proteins, which include two H+ -coupled oligopeptide transporters known as PEPT1 (SLC15A1) and PEPT2 (SLC15A2), along with two peptide/histidine transporters referred to as PHT1 (SLC15A4) and PHT2 (SLC15A3). These transporters play an important role in the drug delivery process in mammalian tissues. They are highly expressed in tissues such as the small intestine, kidney, liver, lung, and eye. PHT1 shows expression in immune cells, especially in B cells and plasmacytoid dendritic cells. The pathophysiological relevance of peptide transporters is emerging to be crucial in various disease conditions, e.g., PEPT1 plays a role in the physiopathology of the gastrointestinal system, particularly in IBD. Upregulated expression of peptide transporters has also been positively related to inflammatory responses. An increasing number of peptide-based drug therapies have been reported to have the potential for development of novel classes of drugs. For example, Carnosine (beta-alanyl-L-histidine) has been demonstrated to act as an antioxidant, antiglycating agent, and neuroprotector. It is transported by PEPT1 and PEPT2, facilitating its protective effects against oxidative stress in neurons and intestinal epithelial cells. Moreover, it has applications in the treatment of multidrug-resistant cancers and has been shown to improve glucose metabolism. This review gives an insight into the functional, physiological and pharmacological importance of proton-coupled oligopeptide transporter.
期刊介绍:
The Journal of Membrane Biology is dedicated to publishing high-quality science related to membrane biology, biochemistry and biophysics. In particular, we welcome work that uses modern experimental or computational methods including but not limited to those with microscopy, diffraction, NMR, computer simulations, or biochemistry aimed at membrane associated or membrane embedded proteins or model membrane systems. These methods might be applied to study topics like membrane protein structure and function, membrane mediated or controlled signaling mechanisms, cell-cell communication via gap junctions, the behavior of proteins and lipids based on monolayer or bilayer systems, or genetic and regulatory mechanisms controlling membrane function.
Research articles, short communications and reviews are all welcome. We also encourage authors to consider publishing ''negative'' results where experiments or simulations were well performed, but resulted in unusual or unexpected outcomes without obvious explanations.
While we welcome connections to clinical studies, submissions that are primarily clinical in nature or that fail to make connections to the basic science issues of membrane structure, chemistry and function, are not appropriate for the journal. In a similar way, studies that are primarily descriptive and narratives of assays in a clinical or population study are best published in other journals. If you are not certain, it is entirely appropriate to write to us to inquire if your study is a good fit for the journal.