EFFECTS OF ORGANIC AND INORGANIC LEAD AND MERCURY ON NEUROTRANSMITTER HIGH-AFFINITY TRANSPORT AND RELEASE MECHANISMS

The effects of two heavy metals upon the high-affinity transport system of certain putative neurotransmitters have been studied in adult mouse brain homogenates. Carbon-linked and free ionic forms of mercury and lead were compared. Tri-n-butyl lead acetate at concentrations as low as 10-6, m severely inhibited the sodium-dependent, energy-requiring uptake of a variety of putative neurotransmitters. Dopamine uptake was more affected than other compounds. Ionic lead (as lead acetate) was several orders of magnitude less toxic than the covalently bound lead compound. Methylmercuric chloride and mercuric chloride had an intermediate inhibitory effect on the high-affinity transport system, significant impairment becoming apparent only at around 10-5, m. Both metals stimulated the release of labeled compounds accumulated by high-affinity transport systems in brain homogenates. This stimulation was greater with tributyl lead acetate than with any other compound tested. The effect was independent of and additive to the stimulatory effect of the calcium ion on neurotransmitter release. Unlike calcium, heavy metals could effect release of transported compounds in the absence of depolarizing conditions. While calcium-mediated release requires over 0.3 mm Ca2+ to be detected, tributyl lead acetate-mediated release of several putative transmitters was apparent at 5 × 10-6, m and mercury compounds had major releasing effects at 5 × 10-5, m. The uptake and release of dopamine was especially strongly affected by covalently bound lead whose effects could be detected at 10-8, m. © 1979.