Involvement of human and canine MRP1 and MRP4 in benzylpenicillin transport

English version

Autoři: Xiaofen Zhao ^aff001; Yangfang Li ^aff001; Kun Du ^aff001; Yuqin Wu ^aff001; Ling Liu ^aff001; Shan Cui ^aff001; Yan Zhang ^aff001; Jin Gao ^aff001; Richard F. Keep ^aff002; Jianming Xiang ^aff002
Působiště autorů: Department of Neonate, Kunming Children’s Hospital, Kunming, China ^aff001; Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan, United States of America ^aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0225702

Souhrn

The blood-brain barrier (BBB) is a dynamic and complex interface between blood and the central nervous system (CNS). It protects the brain by preventing toxic substances from entering the brain but also limits the entry of therapeutic agents. ATP-binding cassette (ABC) efflux transporters are critical for the functional barrier and present a formidable impediment to brain delivery of therapeutic agents including antibiotics. The aim of this study was to investigate the possible involvement of multidrug resistance-associated protein 1 and 4 (MRP1 and MRP4), two ABC transporters, in benzylpenicillin efflux transport using wild-type (WT) MDCKII cells and cells overexpressing those human transporters, as well as non-selective and selective inhibitors. We found that inhibiting MRP1 or MRP4 significantly increased [³H]benzylpenicillin uptake in MDCKII-WT, -MRP1 or –MRP4 cells. Similar results were also found in HepG2 cells, which highly express MRP1 and MRP4, and hCMEC/D3 cells which express MRP1. The results indicate that human and canine MRP1 and MRP4 are involved in benzylpenicillin efflux transport. They could be potential therapeutic targets for improving the efficacy of benzylpenicillin for treating CNS infections since both MRP1 and MRP4 express at human blood-brain barrier.

Klíčová slova:

Antibiotic resistance – Antibiotics – Cancer treatment – Central nervous system – Endothelial cells – RNA synthesis – Toxic agents – Blood-brain barrier

Zdroje

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Involvement of human and canine MRP1 and MRP4 in benzylpenicillin transport

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