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The effects of inorganic mercury in vitro on the release of ( sup 3 H)dopamine from rat striatal synaptosomes: Mechanisms of action

Thesis/Dissertation ·
OSTI ID:5657388
Inorganic mercury (Hg{sup 2+}) increases spontaneous neurotransmitter release from peripheral and central nervous system presynaptic nerve terminals. In rat striatal synaptosomes Hg{sup 2+} ({ge}2 {mu}M) increased spontaneous ({sup 3}H)dopamine release in a concentration-dependent fashion. These effects were not mediated by alterations in transmembrane Na{sup +} and Ca{sup 2+} gradients and could not be blocked by prior inhibition of plasma membrane Na{sup +},K{sup +}-ATPase. Hg{sup 2+} did not increase (Ca{sup 2+}){sub i} regardless of the (Ca{sup 2+}){sub o}. There was no increase in the leakage of lactate dehydrogenase but ({sup 3}H)deoxyglucose-6-phosphate (({sup 3}H)dgluP), fura-2, and {sup 45}Ca{sup 2+} efflux were all elevated by Hg{sup 2+}. There was also a Hg{sup 2+}-induced increase in intrasynaptosomal fura-2 quenching by Mn{sup 2+}. Taken together, these data suggest that Hg{sup 2+} increased the permeability of the plasma membrane to small molecules but not to larger ones. The efflux of ({sup 3}H)dgluP and {sup 45}Ca{sup 2+} was not altered by Co{sup 2+} which effectively blocked all the Hg{sup 2+}-induced increase in ({sup 3}H)dopamine release. Cd{sup 2+} and Pb{sup 2+} were ineffective in blocking this effect suggesting that Hg{sup 2+} does not interact with voltage-dependent Ca{sup 2+} channels to increase spontaneous ({sup 3}H)dopamine release. The Hg{sup 2+} chelator, dimercaptosuccinic acid, was only marginally more effective in reversing Hg {sup 2+}-induced ({sup 3}H)dopamine release than washing in Hg{sup 2+}-free buffer and suggests that Hg{sup 2+} may act at intrasynaptosomal sites, presumably at or near transmitter release mechanisms. Pb{sup 2+}, which is thought to have direct actions on transmitter release from synaptosomes, produced a biphasic increase in spontaneous ({sup 3}H)dopamine release that was not blocked by Co{sup 2+}.
Research Organization:
Cincinnati Univ., OH (United States)
OSTI ID:
5657388
Country of Publication:
United States
Language:
English

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