Abstract
Trace amines (TAs) are present in the central nervous system in which they up-regulate catecholamine release and are implicated in the pathogenesis of addiction, attention-deficit/hyper-activity disorder, Parkinson's disease, and schizophrenia. By using intracellular and patch-clamp recordings from dopaminergic cells in the rat midbrain slices, we report a depressant postsynaptic action of two TAs, beta-phenylethylamine (beta-PEA) and tyramine (TYR) on the GABA(B)-mediated slow inhibitory postsynaptic potential and baclofen-activated outward currents. beta-PEA and TYR activated G-proteins, interfering with the coupling between GABA(B) receptors and G-betagamma-gated inwardly rectifying potassium channels. This is the first demonstration that beta-PEA and TYR depress inhibitory synaptic potentials in neurons of the central nervous system, supporting their emerging role as neuromodulators.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / metabolism
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Cyclic AMP-Dependent Protein Kinases / physiology
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Depression, Chemical
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GABA-B Receptor Antagonists*
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GTP-Binding Protein beta Subunits / physiology*
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GTP-Binding Protein gamma Subunits / physiology*
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Ion Channel Gating
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Male
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Phenethylamines / pharmacology*
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Potassium Channels, Inwardly Rectifying / antagonists & inhibitors*
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Protein Kinase C / physiology
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Rats
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Rats, Wistar
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Receptors, GABA-B / physiology
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Substantia Nigra / drug effects
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Substantia Nigra / physiology
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Synaptic Transmission / drug effects*
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Type C Phospholipases / physiology
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Tyramine / pharmacology*
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Ventral Tegmental Area / drug effects
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Ventral Tegmental Area / physiology
Substances
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GABA-B Receptor Antagonists
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GTP-Binding Protein beta Subunits
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GTP-Binding Protein gamma Subunits
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Phenethylamines
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Potassium Channels, Inwardly Rectifying
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Receptors, GABA-B
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phenethylamine
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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Type C Phospholipases
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Calcium
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Tyramine