S Zevin1, M E Schaner, N P Illsley, K M Giacomini. 1. Division of Clinical Pharmacology and Experimental Therapeutics, University of California San Francisco 94143, USA.
Abstract
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.
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 humanchoriocarcinoma 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.