Multiple components of 2,4-dichlorophenoxyacetic acid uptake by rat choroid plexus

Area of Science:

• Pharmacology
• Neuroscience
• Biochemistry

Background:

• The choroid plexus plays a critical role in regulating cerebrospinal fluid (CSF) composition and protecting the brain.
• Understanding the transport mechanisms of xenobiotics, such as the herbicide 2,4-D, across the choroid plexus is crucial for assessing potential neurotoxicity.

Purpose of the Study:

• To elucidate the specific transporters involved in the initial uptake of 2,4-D into the rat choroid plexus from the CSF.
• To characterize the kinetic properties and inhibitor profiles of these transport mechanisms.

Main Methods:

• Uptake of 2,4-D was measured in intact rat lateral choroid plexus.
• Inhibition studies were performed using various organic anions like estrone sulfate (ES) and p-aminohippurate (PAH).
• Kinetic analysis was employed to determine the different components of 2,4-D uptake.

Main Results:

• Three components of 2,4-D uptake were identified: nonmediated, high-affinity, and low-affinity.
• The high-affinity component was sodium-dependent and sensitive to PAH, consistent with organic anion transporter subtype 3 (Oat3) mediation.
• A distinct PAH-insensitive, sodium-independent component was identified, potentially mediated by Oatp3, and inhibited by ES and other substrates.

Conclusions:

• The initial transport of 2,4-D from CSF to blood involves at least two distinct transporters in the choroid plexus.
• Oat3 mediates a significant portion of 2,4-D uptake, while a second, likely Oatp3, transporter handles the PAH-insensitive component.
• These findings provide insight into the brain's mechanisms for clearing xenobiotics like 2,4-D.