Interactions of lead and calcium on the synaptosomal uptake of dopamine and choline

Exposure of rodents to lead in vivo has been associated with alterations in cholinergic and dopaminergic neurotransmission in the CNS. These effects have been hypothesized to result from competitive interactions between lead and calcium at sites involved in uptake and release of neurotransmitters and their precursors. These experiments reproduced the in vivo observation by in vitro exposure of crude synaptosomal suspensions to lead. Lead-induced inhibition of high affinity choline uptake was mimicked by reduced in vitro calcium concentrations, which suggests that lead's effects on cholinergic function are explainable by the lead-calcium hypothesis. However, inhibition of dopamine uptake was produced only by lead and not by reduced calcium; further additions of calcium did not reverse lead-induced effects on dopamine uptake. Increased calcium concentrations were shown to increase the release of dopamine; lead in the presence of normal calcium concentration did not affect dopamine release. However, more dopamine was released when increased calcium was combined with exposure to 1 × 10^-4 lead. This effect may have resulted from lead's ability to increase the uptake of calcium by synaptosomes. Thus, the interactions between lead and calcium appear to differ in terms of effects on cholinergic and dopaminergic function; in the former, the results suggest a competitive interaction similar to that shown functionally at peripheral cholinergic sites; in the latter, a different role for calcium is hypothesized which may account for the different effects of lead.