Thymidine transport and metabolism in choroid plexus: effect of diazepam and thiopental.
Choroid plexus contains an active transport (influx) and a facilitated diffusion (efflux) system for nucleosides. The ability of diazepam and thiopental to inhibit active transport or facilitated diffusion of thymidine in choroid plexus was measured in vitro under various conditions. When isolated rabbit choroid plexuses were incubated in artificial cerebrospinal fluid containing 1 microM [3H] thymidine for 10 min at 37 degrees C under 95% O2-5% CO2, diazepam (10 microM) and thiopental (500 microM) doubled the tissue-to-medium ratios of [3H] thymidine from 8 to 15 to 16. These results were not due to metabolism or intracellular binding but rather to inhibition of [3H] thymidine efflux from choroid plexus. Diazepam, unlike thiopental, inhibited [3H] thymidine efflux in a concentration-dependent manner. When isolated choroid plexuses were incubated in artificial cerebrospinal fluid containing low concentrations of [3H] thymidine (6 nM) to allow intracellular conversion of [3H] thymidine into [3H] thymidine phosphates and [3H] DNA, both diazepam (10 microM) and thiopental (500 microM) altered [3H] thymidine accumulation and metabolism consistent with inhibition of facilitated diffusion but not active transport of thymidine. These studies provide evidence that, at toxic but not therapeutic concentrations, diazepam and thiopental alter facilitated nucleoside transport in the choroid plexus.
D000818:Animals; D001693:Biological Transport, Active; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002854:Chromatography, Paper; D003975:Diazepam / Q000494:pharmacology*; D004058:Diffusion; D011817:Rabbits; D013874:Thiopental / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism*
D013874:Thiopental; D003975:Diazepam; D013936:Thymidine