Effects of Cd2+, Mn2+, and Al3+ on rat brain synaptosomal uptake of noradrenaline and serotonin |
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Authors: | James CK Lai Louis Lim Alan N Davison |
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Institution: | Miriam Marks Department of Neurochemistry, Institute of Neurology, The National Hospital, London England |
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Abstract: | Cd2+, Mn2+, and Al3+ inhibited synaptosomal amine uptake in a concentration-dependent and time-dependent manner. In the absence of Ca2+, the rank order of inhibition of noradrenaline uptake was: Cd2+ (IC50 = 250 μM) > Al3+ (IC50 = 430 μM) > Mn2+ (IC50 = 1.50 mM), the IC50 being the concentration of metal ions that gave rise to 50% inhibition of uptake. In the presence of 1 mM Ca2+, the rank order of inhibition of uptake was: Al3+ (IC50 = 330 μM) > Cd2+ (IC50 = 540 μM) > (IC50 = 1.5 mM). The rank order of inhibition of serotonin uptake without Ca2+ was: Al3+ (IC50 = 370 μM) > Cd2+ (IC50 = 610 μM) > Mn2+ (IC50 = 3.4 mM) and the rank order in the presence of 1 mM Ca2+ was: Al3+ (IC50 = 290 μM) > Cd2+ (IC50 = 1.5 mM) > Mn2+ (IC50 = 4.0 mM). Ca2+, at 1 mM, definitely antagonized the inhibitory actions of Cd2+ on noradrenaline and serotonin uptake. Al3+ stimulated noradrenaline uptake at concentrations around 20–250 μM but inhibited this uptake at concentrations exceeding 300 μM in a dose-related fashion. Ca2+, at 1 mM, enhanced both the stimulatory and inhibitory effects of Al3+. Ca2+ also enhanced the inhibitory actions of Al3+ on seotonin uptake. These results, in conjunction with those we have previously published, suggest that Cd2+, Mn2+, and Al3+ exert differential and selective effects on the structure and function of synaptosomal membranes. |
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Keywords: | Address reprint requests to Dr Louis Lim Department of Neurochemistry Institute of Neurology The National Hospital Quseen Square London WC1N 3B6 England |
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