Facilitation of Acetylcholine Signaling by the Dithiocarbamate Fungicide Propineb
| Autor: | Amalia Di Nucci, Corrado L. Galli, Marcello Tonini, Marina Marinovich, Marco Binaglia, Barbara Viviani, Gianluigi D'Agostino, Valérie Capra, Laura Anselmi, Emanuela Corsini |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty Guinea Pigs Neuromuscular Junction Myenteric Plexus Toxicology Hexamethonium Neuroblastoma chemistry.chemical_compound Ileum Internal medicine Tumor Cells Cultured medicine Animals Humans Myocyte Muscle Skeletal Receptor Zineb Dose-Response Relationship Drug Skeletal muscle Muscle Smooth Long-term potentiation General Medicine Bungarotoxins Acetylcholine Electric Stimulation Fungicides Industrial Endocrinology Nicotinic agonist medicine.anatomical_structure Cholinergic Fibers chemistry Cholinergic Muscle Contraction Signal Transduction medicine.drug |
| Zdroj: | Chemical Research in Toxicology. 15:26-32 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/tx015538c |
| Popis: | Dithiocarbamates (DTCs) are used mainly in agriculture as pesticides and as alcohol deterrent drugs. Neurological complications as well as movement disorders characterized by plastic rigidity, muscle twitch and paralysis are the prevailing symptoms in chronically exposed animals and humans. We investigated whether propineb interfered with peripheral cholinergic transmission in various isolated model systems. In electrically stimulated longitudinal muscle-myenteric plexus preparations (LMMPs), propineb (0.01-1000 nM) concentration-dependently enhanced the amplitude of both neurogenic twitch contractions and tritiated acetylcholine ([3H]ACh) release. The maximum percent increase was achieved by 10 nM propineb and was 19% and 14%, respectively. The effect on twitch contractions was partially antagonized by hexamethonium, a ganglionic nicotinic receptor blocker. In unstimulated LMMPs, propineb (10 pM, 10 nM, 10 microM) did not affect contractions to applied acetylcholine (ACh; 1 nM-10 microM), a finding indicating that propineb has no anticholinesterase activity. In human neuroblastoma cells (SH-SY5Y), propineb facilitated ACh release evoked by KCl depolarization. The increase in ACh release was not associated with detectable alterations of intracellular Ca2+([Ca2+]i) homeostasis. Binding studies carried out with alpha-bungarotoxin in striated muscle cells (L6) failed to demonstrate any influence of propineb on both affinity and capacity of skeletal muscle nicotinic receptors. In conclusion, propineb was found to interfere with cholinergic transmission in LMMPs and SH-SY5Y cells. In LMMPs, the potentiation of cholinergic transmission is partly dependent on the activation of ganglionic nicotinic receptors. Other targets relevant to cholinergic transmission seem not to be affected by propineb. |
| Databáze: | OpenAIRE |
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