Trace amines depress GABA B response in dopaminergic neurons by inhibiting G-betagamma-gated inwardly rectifying potassium channels.
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.
Federici
Mauro
M
Department of Experimental Neurology, S. Lucia Foundation I.R.C.C.S., Via Ardeatina 306, 00179 Rome, Italy.
Geracitano
Raffaella
R
Tozzi
Alessandro
A
Longone
Patrizia
P
Di Angelantonio
Silvia
S
Bengtson
C Peter
CP
Bernardi
Giorgio
G
Mercuri
Nicola B
NB
D000818:Animals; D002118:Calcium / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D003864:Depression, Chemical; D058788:GABA-B Receptor Antagonists; D044387:GTP-Binding Protein beta Subunits / Q000502:physiology*; D044388:GTP-Binding Protein gamma Subunits / Q000502:physiology*; D015640:Ion Channel Gating; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000502:physiology; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D010738:Type C Phospholipases / Q000502:physiology; D014439:Tyramine / Q000494:pharmacology*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
D058788:GABA-B Receptor Antagonists; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D010627:Phenethylamines; D024661:Potassium Channels, Inwardly Rectifying; D018080:Receptors, GABA-B; C029261:phenethylamine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium; D014439:Tyramine