Antagonistic effect of dopamine structural analogues on human GABA?1 receptor.

ABSTRACT: GABAergic and dopaminergic pathways are co-localized in several areas of the central nervous system and recently several reports have shown co-release of both neurotransmitters. The GABA-A receptor (? and ?1 subunits) is modulated by dopamine (DA) and, interestingly, GABA?1 can be modulated by several biogenic amines. Here we explored the effects of the metabolites of the dopaminergic pathway and other structural analogues of DA on GABA?1 and the DA gated ion channel (LGC-53) from Caenorhabditis elegans expressed in Xenopus laevis oocytes. Our findings show an antagonistic effect of the metabolite 3-Methoxytyramine (3-MT, IC50?=?285?±?30?µM) with similar potency compared to DA on induced GABA currents; however, it was inactive on LGC-53. The structural DA analogues and metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 2-phenylethylamine (?-PEA) and 4-amino-1-butanol (4-AM-1-OH), antagonized GABA?1 currents, whereas ?-PEA acted as partial agonists on LGC-53, indicating that the putative binding sites of both receptors may share structural characteristics. These results suggest that the DA metabolites 3-MT, DOPAC and HVA modulate GABA?1 and possibly affect the activity of the receptors that include this subunit in vivo.

SUBMITTER: Alaniz-Palacios A 

PROVIDER: S-EPMC5727059 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature