ArticleMolecular pharmaceutics2010
Effect of HEPES buffer on the uptake and transport of P-glycoprotein substrates and large neutral amino acids.
Article in Molecular pharmaceutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
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- Theoretical Prediction of the Complex P-Glycoprotein Substrate Efflux Based on the Novel Hierarchical Support Vector Regression Scheme.Molecules (Basel, Switzerland) · 2018Article
- Development of a direct contact astrocyte-human cerebral microvessel endothelial cells blood-brain barrier coculture model.The Journal of pharmacy and pharmacology · 2017Article
- Comparison of cell-based versus cell-free mammalian systems for the production of a recombinant human bone morphogenic growth factor.Engineering in life sciences · 2017Article
- Honokiol affects melanoma cell growth by targeting the AMP-activated protein kinase signaling pathway.American journal of surgery · 2014Article
- An electrically tight in vitro blood-brain barrier model displays net brain-to-blood efflux of substrates for the ABC transporters, P-gp, Bcrp and Mrp-1.The AAPS journal · 2014Article
- Allosteric modulation of alpha4beta2 nicotinic acetylcholine receptors by HEPES.European journal of pharmacology · 2014Article
- Binary and ternary combinations of anti-HIV protease inhibitors: effect on gene expression and functional activity of CYP3A4 and efflux transporters.Drug metabolism and drug interactions · 2014Article
- Bitter melon extracts enhance the activity of chemotherapeutic agents through the modulation of multiple drug resistance.Journal of pharmaceutical sciences · 2013Article
- A simple medium enables bovine embryos to be held for seven days at 4°C.Scientific reports · 2013Article
- Differential effect of P-gp and MRP2 on cellular translocation of gemifloxacin.International journal of pharmaceutics · 2011Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
HEPES has been widely employed as an organic buffer agent in cell culture medium as well as uptake and transport experiments in vitro. However, concentrations of HEPES used in such studies vary from one laboratory to another. In this study, we investigated the effect of HEPES on the uptake and bidirectional transport of P-gp substrates employing both Caco-2 and MDCK-MDR1 cells. ATP-dependent uptake of glutamic acid was also examined. ATP production was further quantified applying ATP Determination Kit. An addition of HEPES to the growth and incubation media significantly altered the uptake and transport of P-gp substrates in both Caco-2 and MDCK-MDR1 cells. Uptake of P-gp substrates substantially diminished as the HEPES concentration was raised to 25 mM. Bidirectional (A-B and B-A) transport studies revealed that permeability ratio of P(appB-A) to P(appA-B) in the presence of 25 mM HEPES was significantly higher than control. The uptake of phenylalanine is an ATP-independent process, whereas the accumulation of glutamic acid is ATP-dependent. While phenylalanine uptake remained unchanged, glutamic acid uptake was elevated with the addition of HEPES. Verapamil is an inhibitor of P-gp mediated uptake; elevation of cyclosporine uptake in the presence of 5 muM verapamil was compromised by the presence of 25 mM HEPES. The results of ATP assay indicated that HEPES stimulated the production of ATP. This study suggests that the addition of HEPES in the medium modulated the energy dependent efflux and uptake processes. The effect of HEPES on P-gp mediated drug efflux and transport may provide some mechanistic insight into possible reasons for inconsistencies in the results reported from various laboratories.
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