Effects of methylmercury on neurotransmitter release from rat brain synaptosomes
| Autor: | G.P. Cooper, Robert D. Greenland, Daniel J. Minnema |
|---|---|
| Rok vydání: | 1989 |
| Předmět: |
Male
Cell Membrane Permeability Membrane permeability ATPase chemistry.chemical_element Action Potentials Glucose-6-Phosphate Calcium In Vitro Techniques Toxicology Aminobutyric acid chemistry.chemical_compound medicine Animals Neurotransmitter Pharmacology Calcium metabolism Synaptosome Neurotransmitter Agents biology Glucosephosphates Brain Methylmercury Compounds Mitochondria Rats Biochemistry chemistry biology.protein Biophysics Potassium Acetylcholine medicine.drug Synaptosomes |
| Zdroj: | Toxicology and applied pharmacology. 99(3) |
| ISSN: | 0041-008X |
| Popis: | Although the effects of methylmercury (MeHg) at the neuromuscular junction have been well characterized, similar studies employing CNS preparations and transmitters have been limited. We found that MeHg (0.5–5.0 μM) produced a concentration-dependent increase in the spontaneous release of [ 3 H]dopamine, γ-[ 3 H]aminobutyric acid, and [ 3 H]acetylcholine from synaptosomes isolated from rat brain striatum, cortex, and hippocampus, respectively. At these same concentrations MeHg did not attenuate calcium-dependent depolarization-evoked 3 H-transmitter release. MeHg did not appear to induce calcium influx into the nerve terminal since the increase in release persists in the absence of extrasynaptosomal calcium. The increase in spontaneous transmitter release induced by MeHg persisted in the presence of low extrasynaptosomal sodium, suggesting that MeHg's effects on release are not mediated by either Na + , K + -ATPase inhibition or selective increases in membrane sodium permeability. MeHg produced only a very small increase in 45 Ca efflux from synaptosomes preloaded with 45 Ca, whereas these same MeHg concentrations produced large increases in 45 Ca efflux from preloaded isolated mitochondria. MeHg did increase the efflux of [ 3 H]deoxyglucose phosphate from synaptosomes. An increase in the efflux of [ 3 H]deoxyglucose phosphate is believed to reflect an increase in neuronal membrane permeability. The quantitative and temporal aspects of the MeHg-induced [ 3 H]-deoxyglucose phosphate efflux were similar to those observed for MeHg-induced neurotransmitter release. These data suggest that the increase in spontaneous transmitter release induced by MeHg is mainly the result of transmitter leakage that occurs subsequent to MeHg-induced increases in synaptosomal membrane permeability. However, these results cannot exclude possible effects of MeHg on intrasynaptosomal calcium homeostasis. |
| Databáze: | OpenAIRE |
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