Abstract
In vitro exposure to tetraethyllead (Et 4Pb, 10 μM) did not alter the release of [ 3H]dopamine (DA), [ 3H]acetylcholine (ACh), or [ 3 H]γ- aminobutyric acid (GABA) from superfused synaptosomes isolated from rat brain striatum, hippocampus, and cortex, respectively. On the other hand, a concentration-dependent increase in the spontaneous release of these transmitters was observed following exposure to triethyllead (Et 3Pb, 0.1–10 μM). The magnitude of 1 μM Et 3Pb-induced [ 3H]DA release was 5-fold greater than that observed for [ 3H]ACh or [ 3H]GABA release. Removal of [Ca 2+] e did not alter the Et 3Pb-induced increase in the release of these three transmitter substances, nor did Et 3Pb alter synaptosomal 45Ca efflux. Et ePb-induced [ 3H]ACh and [ 3H]GABA release, but not [ 3H]DA release, was blocked by lowering [Na +] e from 140 to 50 mM. Similarly, the release of [ 3H]ACh and [ 3H]GABA, but not [ 3H]DA, induced by either Na,K-ATPase inhibition or veratridine (a Na +-ionophore), was attenuated by lowering [Na +] e from 140 to 50 mM. However, Et 3Pb did not inhibit isolated synaptic membrane Na,K-ATPase, nor did the magnitude or temporal patterns of Et 3Pb-induced transmitter release resemble transmitter release induced by Na,K-ATPase inhibition. Et 3Pb and veratridine, but not Na,K-ATPase inhibition, produced an increase in synaptosomal [ 3H]deoxyglucose phosphate (dGluP) efflux, suggesting that both compounds increase membrane permeability. A Et 3Pb-induced increase in membrane permeability is further supported by electrophysiological studies using the frog neuromuscular junction in which Et 3Pb was found to reduce both the input resistance and membrane potential of muscle cells. As with [ 3H]ACh and [ 3H]GABA release, the Et 3Pb-induced increase in synaptosomal [ 3H]dGluP efflux was attenuated by lowering [Na +] e. The membrane Na + channel blocker, tetrodotoxin (TTX), delayed, but did not block, the Et 3Pb-induced increase in [ 3H]ACh release, whereas TTX blocked the release of [ 3H]ACh induced by veratridine. Unlike Et 3Pb, a differential effect of veratridine on the magnitude of [ 3H]DA release was not observed. These experiments suggest that the Et 3Pb-induced increase in [ 3H]ACh and [ 3H]GABA release is due to an increase in membrane permeability. The mechanisms underlying the differential sensitivity of [ 3H]DA release to Et 3Pb are unresolved.
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