Investigation of the GPR39 zinc receptor following inhibition of monoaminergic neurotransmission and potentialization of glutamatergic neurotransmission

TY - JOUR

T1 - Investigation of the GPR39 zinc receptor following inhibition of monoaminergic neurotransmission and potentialization of glutamatergic neurotransmission

AU - Młyniec, Katarzyna

AU - Gaweł, Magdalena

AU - Librowski, Tadeusz

AU - Reczyński, Witold

AU - Bystrowska, Beata

AU - Holst, Birgitte

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.brainresbull.2015.04.005

DO - 10.1016/j.brainresbull.2015.04.005

M3 - Journal article

C2 - 25917396

SN - 0361-9230

VL - 115

SP - 23

EP - 29

JO - Brain Research Bulletin

JF - Brain Research Bulletin

ER -