PT  - JOURNAL ARTICLE
AU  - MeeRa Hong
AU  - Lyanne Schlichter
AU  - Reina Bendayan
TI  - A Na<sup>+</sup>-Dependent Nucleoside Transporter in Microglia
DP  - 2000 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 366--374
VI  - 292
IP  - 1
4099  - http://jpet.aspetjournals.org/content/292/1/366.short
4100  - http://jpet.aspetjournals.org/content/292/1/366.full
SO  - J Pharmacol Exp Ther2000 Jan 01; 292
AB  - In the central nervous system, HIV-1 has a defined tropism for brain macrophages and microglia. Nucleoside analog drugs such as zidovudine improve the clinical and neuropsychological functions in HIV-demented patients. Multiple carrier-mediated transport systems can play an important role in the membrane permeation of nucleosides and nucleoside analog drugs in a number of cells. The purpose of this project was to characterize the uptake properties of the pyrimidine nucleoside probe thymidine by a continuous rat microglia cell line (MLS-9) grown as a monolayer on an impermeable substratum. Approximately 50% of thymidine (10 μM) uptake by the monolayer cells was found to be Na+dependent. Kinetics of specific thymidine uptake showed a single saturation system (Km = 44 μM at 37°C) and a Na+/thymidine stoichiometry of 2:1. Pyrimidine and purine nucleoside probes (50 μM) exerted a competitive inhibitory effect on specific thymidine uptake withKi values of 40, 38, 45, and 39 μM for adenosine, uridine, guanosine, and cytidine, respectively. In addition, nucleoside analog drugs significantly decreased specific thymidine uptake, with IC50 values of 135.1 μM for abacavir and 0.6 μM for zidovudine, which inhibited in a noncompetitive manner. These results suggest that a Na+-dependent nucleoside transport system is present in rat microglia and that long-range interactions between antiretroviral nucleoside analog drugs and the nucleoside substrates may occur at the transporter sites. The American Society for Pharmacology and Experimental Therapeutics