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Guanidine transport in a human choriocarcinoma cell line (JAR)
S Zevin1, M E Schaner, N P Illsley
1Division of Clinical Pharmacology and Experimental Therapeutics, University of California San Francisco 94143, USA.
Purpose:
Many endogenous substances and xenobiotics are organic cations. Transplacental transport of organic cations is an important determinant of the delivery of these compounds to the fetus. The aim of this study was to determine the mechanisms of organic cation transport using the human choriocarcinoma cell line (JAR) as a model system with [14C]guanidine as a ligand.
Methods:
Uptake studies of [14C]guanidine were carried out in JAR cell monolayers on day 2 after plating.
Results:
[14C]guanidine uptake was temperature dependent, saturable (Km = 167 microM) and inhibited by many organic cations including amiloride, cimetidine, quinine, quinidine and nicotine. [14C]guanidine uptake exhibited a counterflux phenomenon indicative of a carrier-mediated process. The uptake of [14C]guanidine was sodium and pH-independent and could be driven by an inside-negative membrane potential difference.
Conclusions:
This is the first demonstration of an electrogenic guanidine transporter in a human cell culture model. This transporter may play a role in the transplacental transport of many clinically used drugs and xenobiotics.
Insights
Researchers identified an electrogenic guanidine transporter in human cells, crucial for transporting organic cations across the placenta. This finding impacts understanding fetal exposure to drugs and xenobiotics.
Area of Science:
- Pharmacology
- Cell Biology
- Physiology
Background:
- Organic cations, including endogenous substances and xenobiotics, are transported across the placenta.
- Efficient transplacental transport is critical for fetal exposure to these compounds.
Purpose of the Study:
- To investigate the transport mechanisms of organic cations using the JAR human choriocarcinoma cell line.
- To characterize the transport of [14C]guanidine as a model organic cation.
Main Methods:
- Uptake studies of [14C]guanidine were performed in JAR cell monolayers.
- Transport characteristics including temperature dependence, saturation kinetics, and inhibition by other organic cations were assessed.
Main Results:
- [14C]guanidine uptake demonstrated temperature dependence and saturability (Km = 167 microM).
- Uptake was inhibited by various organic cations and showed a counterflux phenomenon, indicating carrier-mediated transport.
- Transport was independent of sodium and pH but driven by membrane potential, suggesting an electrogenic transporter.
Conclusions:
- This study demonstrates, for the first time, an electrogenic guanidine transporter in a human cell culture model.
- This identified transporter likely plays a significant role in the transplacental transfer of numerous drugs and xenobiotics.