Investigation of the GPR39 zinc receptor following inhibition of monoaminergic neurotransmission and potentialization of glutamatergic neurotransmission.
Zinc can regulate neural function in the brain via the GPR39 receptor. In the present study we investigated whether inhibition of serotonin, noradrenaline and dopamine synthesis and potentialization of glutamate, via administration of p-chlorophenylalanine (pCPA), α-methyl-p-tyrosine (αMT) and N-methyl-D-aspartatic acid (NMDA), respectively, would cause changes in GPR39 levels. Western blot analysis showed GPR39 up-regulation following 3-day administration of αMT and NMDA in the frontal cortex, and GPR39 down-regulation following 10-day administration of pCPA, αMT, and NMDA in the hippocampus of CD-1 mice. There were no changes in serum zinc levels. Additionally, we investigated tryptophan, tyrosine and glutamate concentrations in the hippocampus and frontal cortex of GPR39 knockout (GPR39 KO) mice. Liquid chromatography-mass spectrometry (LC-MS) showed a significant decrease in tryptophan and tyrosine, but not in glutamate concentrations in the hippocampus of GPR39 KO mice. There were no changes in the frontal cortex between GPR39 KO and wild type. These results indicate a possible role of the GPR39 receptor in monoaminergic and glutamatergic neurotransmission, which plays an important role in the pathophysiology of depression.
Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland. Electronic address: katarzyna.mlyniec@uj.edu.pl.
Katarzyna
K
Młyniec
Department of Radioligands, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland.
Magdalena
M
Gaweł
Department of Radioligands, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland.
Tadeusz
T
Librowski
Faculty of Material Science and Ceramics, AGH University of Science and Technology, Mickiewicza 30, PL 30-059 Kraków, Poland.
Witold
W
Reczyński
Department Toxicology, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland.
Beata
B
Bystrowska
Department of Neuroscience and Pharmacology University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen, Denmark.
Birgitte
B
Holst
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D010134:Fenclonine / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014364:Tryptophan / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D015032:Zinc / Q000097:blood; D019805:alpha-Methyltyrosine / Q000494:pharmacology
C512928:GPR39 protein, mouse; D018377:Neurotransmitter Agents; D043562:Receptors, G-Protein-Coupled; D012701:Serotonin; D018698:Glutamic Acid; D014443:Tyrosine; D016202:N-Methylaspartate; D019805:alpha-Methyltyrosine; D014364:Tryptophan; D015032:Zinc; D010134:Fenclonine; D004298:Dopamine; D009638:Norepinephrine
Depression; GPR39; NMDA; Noradrenaline; Serotonine; Zinc