ArticleAntimicrobial agents and chemotherapy2009
Identification of the efflux transporter of the fluoroquinolone antibiotic ciprofloxacin in murine macrophages: studies with ciprofloxacin-resistant cells.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 32 citations in OpenAlex.
- Effects of fluoroquinolone antibiotics on extracellular matrix-related phenotypes in tendon cells.Scientific reports · 2026Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Pharmacokinetic herb-drug interactions: Altered systemic exposure and tissue distribution of ciprofloxacin, a substrate of multiple transporters, after combined treatment withFrontiers in pharmacology · 2022Article
- Investigation of the Importance of Multidrug Resistance-Associated Protein 4 (Mrp4/Abcc4) in the Active Efflux of Anionic Drugs Across the Blood-Brain Barrier.Journal of pharmaceutical sciences · 2017Article
- Glucuronidation: driving factors and their impact on glucuronide disposition.Drug metabolism reviews · 2017Review
- Effect of Multi Drug Resistance Protein 4 (MRP4) Inhibition on the Pharmacokinetics and Pharmacodynamics of Ciprofloxacin in Normal and Rats with LPS-Induced Inflammation.European journal of drug metabolism and pharmacokinetics · 2016Article
- A "Double-Edged" Scaffold: Antitumor Power within the Antibacterial Quinolone.Current medicinal chemistry · 2016Review
- Pharmacological characterization of 7-(4-(Piperazin-1-yl)) ciprofloxacin derivatives: antibacterial activity, cellular accumulation, susceptibility to efflux transporters, and intracellular activity.Pharmaceutical research · 2014Article
- A 30-years review on pharmacokinetics of antibiotics: is the right time for pharmacogenetics?Current drug metabolism · 2014Review
- Article
- Prodrug strategies in ocular drug delivery.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2012Review
- Intestinal ciprofloxacin efflux: the role of breast cancer resistance protein (ABCG2).Drug metabolism and disposition: the biological fate of chemicals · 2011Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
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Abstract
Ciprofloxacin, the most widely used totally synthetic antibiotic, is subject to active efflux mediated by a MRP-like transporter in wild-type murine J774 macrophages. To identify the transporter among the seven potential Mrps, we used cells made resistant to ciprofloxacin obtained by long-term exposure to increasing drug concentrations (these cells show less ciprofloxacin accumulation and provide a protected niche for ciprofloxacin-sensitive intracellular Listeria monocytogenes). In the present paper, we first show that ciprofloxacin-resistant cells display a faster efflux of ciprofloxacin which is inhibited by gemfibrozil (an unspecific MRP inhibitor). Elacridar, at a concentration known to inhibit P-glycoprotein and breast cancer resistance protein (BCRP), only slightly increased ciprofloxacin accumulation, with no difference between resistant and wild-type cells. Analysis at the mRNA (real-time PCR) and protein (Western blotting) levels revealed an overexpression of Mrp2 and Mrp4. Mrp4 transcripts, however, were overwhelmingly predominant (45% [wild-type cells] to 95% [ciprofloxacin-resistant cells] of all Mrp transcripts tested [Mrp1 to Mrp7]). Silencing of Mrp2 and Mrp4 with specific small interfering RNAs showed that only Mrp4 is involved in ciprofloxacin transport in both ciprofloxacin-resistant and wild-type cells. The study therefore identifies Mrp4 as the most likely transporter of ciprofloxacin in murine macrophages but leaves open a possible common upregulation mechanism for both Mrp4 and Mrp2 upon chronic exposure of eukaryotic cells to this widely used antibiotic.
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