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Fluorescein-methotrexate transport in rat choroid plexus analyzed using confocal microscopy
Christopher M Breen1, Destiny B Sykes, Carsten Baehr
1Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
American Journal of Physiology. Renal Physiology
|May 6, 2004
Summary
The choroid plexus (CP) actively transports fluorescein-methotrexate (FL-MTX) from cerebrospinal fluid (CSF) to blood. This process involves Na-dependent uptake and basolateral efflux, crucial for clearing toxins.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- The choroid plexus (CP) is vital for removing toxic metabolites and xenobiotics from cerebrospinal fluid (CSF) into the blood.
- Understanding CP transport mechanisms is key to managing neurological conditions and drug delivery.
Purpose of the Study:
- To investigate the transport mechanism of the organic anion fluorescein-methotrexate (FL-MTX) across the intact rat choroid plexus (CP).
- To elucidate the specific steps and transporters involved in the transepithelial transport of FL-MTX from CSF to blood.
Main Methods:
- Confocal microscopy and quantitative image analysis were used to track FL-MTX.
- Transport was studied in intact rat CP preparations under various conditions (e.g., altered ion concentrations, presence of inhibitors).
Main Results:
- Concentrative transport of FL-MTX from CSF to blood was observed, with higher concentrations in subepithelial and vascular spaces than in the CSF.
- Apical uptake of FL-MTX was saturable and Na-dependent.
- Digoxin and MK-571 inhibited basolateral efflux, leading to increased cellular accumulation, suggesting specific transporter involvement.
Conclusions:
- Transepithelial transport of FL-MTX involves a two-step mediated process: Na-dependent uptake at the apical membrane and electroneutral efflux at the basolateral membrane.
- Potential transporters include Oatp2 for uptake and Mrp1 for efflux.
- This highlights the CP's role in xenobiotic clearance and provides insights into transporter function.