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Trace amines depress D(2)-autoreceptor-mediated responses on midbrain dopaminergic cells.

Abstract：

BACKGROUND AND PURPOSE:Although trace amines (TAs) are historically considered 'false neurotransmitters' on the basis of their ability to induce catecholamine release, there is evidence that they directly affect neuronal activity via TA receptors, ligand-gated receptor channels and/or sigma receptors. Here, we have investigated the effects of two TAs, tyramine (TYR) and beta-phenylethylamine (beta-PEA), on electrophysiological responses of substantia nigra pars compacta (SNpc) dopaminergic cells to the D(2) receptor agonist, quinpirole. EXPERIMENTAL APPROACH:Electrophysiological recordings of D(2) receptor-activated G-protein-gated inward rectifier K(+) channel (GIRK) currents were performed on dopaminergic cells from midbrain slices of mice and on Xenopus oocytes expressing D(2) receptors and GIRK channels. KEY RESULTS:TYR and beta-PEA reversibly reduced D(2) receptor-activated GIRK currents in a concentration-dependent manner on SNpc neurones. The inhibitory effect of TAs was still present in transgenic mice with genetically deleted TA(1) receptors and they could not be reproduced by the selective TA(1) agonist, o-phenyl-3-iodotyramine (O-PIT). Pretreatment with antagonists of sigma1 and sigma2 receptors did not block TA-induced effects. In GTPgammaS-loaded neurones, the irreversibly-activated GIRK-current was still reversibly reduced by beta-PEA. Moreover, beta-PEA did not affect basal or dopamine-evoked GIRK-currents in Xenopus oocytes. CONCLUSIONS AND IMPLICATIONS:TAs reduced dopamine-induced responses on SNpc neurones by acting at sites different from TA(1), sigma-receptors, D(2) receptors or GIRK channels. Although their precise mechanism of action remains to be identified, TAs, by antagonizing the inhibitory effects of dopamine, may render dopaminergic neurones less sensitive to autoreceptor feedback inhibition and hence enhance their sensitivity to stimulation.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Ledonne A,Federici M,Giustizieri M,Pessia M,Imbrici P,Millan MJ,Bernardi G,Mercuri NB

doi

10.1111/j.1476-5381.2010.00792.x

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

1509-20

issue

eissn

0007-1188

issn

1476-5381

pii

BPH792

journal_volume

160

pub_type

杂志文章

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Trace amines depress D(2)-autoreceptor-mediated responses on midbrain dopaminergic cells.