Biology of Peptide Transporter 2 in Mammals: New Insights into Its Function, Structure and Regulation

Abstract

Peptide transporter 2 (PepT2) in mammals plays essential roles in the reabsorption and conservation of peptide-bound amino acids in the kidney and in maintaining neuropeptide homeostasis in the brain. It is also of significant medical and pharmacological significance in the absorption and disposing of peptide-like drugs, including angiotensin-converting enzyme inhibitors, β-lactam antibiotics and antiviral prodrugs. Understanding the structure, function and regulation of PepT2 is of emerging interest in nutrition, medical and pharmacological research. In this review, we provide a comprehensive overview of the structure, substrate preferences and localization of PepT2 in mammals. As PepT2 is expressed in various organs, its function in the liver, kidney, brain, heart, lung and mammary gland has also been addressed. Finally, the regulatory factors that affect the expression and function of PepT2, such as transcriptional activation and posttranslational modification, are also discussed.

Effect of Cimetidine on Metformin Pharmacokinetics and Endogenous Metabolite Levels in Rats

“…The quinoline and quinolone serve as building blocks for complex natural compounds, which are widespread in nature and can be extracted from various sources, including plants such as the cinchona tree's bark, animals, and microorganisms (Heeb et al, 2011). The metabolomics data also identified several peptides as endogenous cationic substrates; however, these peptides might not be ideal candidates due to the possibility of involvement in renal reabsorption through peptide transporters (PEPT1 and PEPT2) (Wang et al, 2022). Additionally, some proposed peptides have large molecular weights, whereas only small organic cation molecules not exceeding 500 Dalton can be transported through cationic transporters (Hendrickx et al, 2013).…”

Recent Advances in Micro- and Nano-Drug Delivery Systems Based on Natural and Synthetic Biomaterials

“…Respiratory epithelial cells are in charge of both the production of airway-lining fluid and the regulation of airway tone. A non-invasive delivery of therapeutic medicines may be achieved via pulmonary administration, which has a high permeability, a large absorptive surface area (about 70-140 m 2 in human adults with an exceptionally thin absorptive mucosal membrane), and a good blood supply [277][278][279]. Chlorofluorocarbons propellants are also being phased out of industrial and residential applications across the world, which has sparked the creation of novel substitutes.…”

Pharmacokinetics of Antibacterial Agents in the Elderly: The Body of Evidence

“…Estimation of BCRP expression in the liver demonstrated the same decline with age, being the lowest in the elderly compared with adults and children [ 82 ]. Aging also may also affect the expression of peptide transporters 1 and 2 (PepT1 and 2), which are involved in the uptake of di- or tripeptide substrates in such locations, as the intestine, kidneys, bile duct epithelium (PepT1), brain, lung, and mammary gland (PepT2) [ 83 , 84 ]. PepT1 and Pept2 expression may be altered in the presence of age-related diseases including diabetes mellitus (downregulation of PepT1) and obesity (leptin-dependent activation of PepT1 activity and expression) [ 83 ].…”