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Abstract: The effects of lead and mercury on [3H]-histamine uptake by cultured astroglial and endothelial cells of rat brain were studied. Experimental data showed that both metal ions inhibited the uptake in both cell types of concentrations as low as 1–10 μM. The effects were consistent with non/competitive inhibitions. With either lead or mercury exposure, the inhibition of the uptake was greater in astroglial than in cerebral endothelial cells. Contrary to the above findings, 100 μM of mercuric chloride produced stimulation of histamine uptake and this stimulation was much more pronounced in cultured cerebral endothelial cells than in astroglial cells. Inhibition of [3H]-histamine uptake by lead acetate and mercuric chloride was considered to be association with a loss of the transmembrane Na+ and/or K+ gradient while stimulation of the uptake by high concentration of mercury might be related to a direct effect on histamine transporter. It is noteworthy, that cultured astroglial cells, derived from neonatal rat brain, are much more sensitive to the toxic effects of these heavy metal ions than cultured endothelial cells derived from the brain capillaries of the same species of animals.