Ca2+‐Surrogate Action of Pb2+ on Acetylcholine Release from Rat Brain Synaptosomes

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Abstract
The effect of lead ions on the release of acetylcholine (ACh) was investigated in intact and digitonin‐permeabilized rat cerebrocortical synaptosomes that had been prelabeled with [3H]choline. Release of ACh was inferred from the release of total 3H label or by determination of [3H]ACh. Application of 1 μM Pb2+ to intact synaptosomes in Ca2+‐deficient medium induced 3H release, which was enhanced by K+ depolarization. This suggests that entry of Pb2+ into synaptosomes and Pb2+‐induced ACh release can be augmented by activation of the voltage‐gated Ca2+ channels in nerve terminals. The lead‐induced release of [3H]ACh was blocked by treatment of synaptosomes with vesamicol, which prevents uptake of ACh into synaptic vesicles without affecting its synthesis in the synaptoplasm. This indicates that Pb2+ selectively activates the release of a vesicular fraction of the transmitter with little or no effect on the leakage of cytoplasmic ACh. Application of 1–50 nM (EC50± 4 nM) free Pb2+ to digitonin‐permeabilized synaptosomes elicited release of 3H label that was comparable with the release induced by 0.2–5 μM (EC50± 0.5 μM) free Ca2+. This suggests that Pb2+ triggers transmitter exocytosis directly and that it is a some 100 times more effective activator of exocytosis than is the natural agonist Ca2+.