PMID- 28966248
OWN - NLM
STAT- MEDLINE
DCOM- 20180612
LR  - 20191210
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 40
IP  - 10
DP  - 2017
TI  - Pharmacological Activation Gi/o Protein Increases Glial Cell Line-Derived 
      Neurotrophic Factor Production through Fibroblast Growth Factor Receptor and 
      Extracellular Signal-Regulated Kinase Pathway in Primary Cultured Rat Cortical 
      Astrocytes.
PG  - 1759-1766
LID - 10.1248/bpb.b17-00383 [doi]
AB  - A significant reduction of glial cell line-derived neurotrophic factor (GDNF) has 
      been identified in the pathophysiology of neurodegenerative and neuropsychiatric 
      disorders. Thus, clarification of the mechanism of GDNF production, and 
      modulating brain GDNF levels could be a novel therapeutic approach. A previous 
      study demonstrated that antidepressant amitriptyline-induced GDNF production was 
      significantly inhibited by pertussis toxin (PTX), a Gi/o protein inhibitor in 
      astrocytes, the main source of GDNF in the brain. However, it is not known 
      whether direct activation of Gi/o protein might induce GDNF expression, and what 
      mechanisms might be involved after Gi/o protein activation. The current study 
      investigated Gi/o protein-initiated GDNF production in rat cortical astrocytes 
      using activators that directly activate Gi/o protein, mastoparan and 
      compound48/80. Treatment of astrocytes with either mastoparan or compound48/80 
      increased GDNF mRNA expression at 3 and 6 h, and GDNF protein release at 24 h. 
      Treatment of astrocyte with either mastoparan or compound48/80 increased 
      brain-derived neurotrophic factor (BDNF) mRNA expression as well as GDNF. 
      Mastoparan and compound48/80-induced GDNF mRNA expression were significantly 
      inhibited by not only PTX, but also fibroblast growth factor receptor (FGFR) 
      inhibitors, and mitogen-activated protein kinase (MAPK)/extracellular 
      signal-regulated kinase (ERK) kinase (MEK) inhibitor. In fact, both FGFR 
      substrate2alpha (FRS2alpha) and ERK phosphorylation were increased by treatment with 
      either mastoparan or compound48/80, and these were significantly blocked by PTX. 
      Thus, direct, receptor-independent Gi/o protein activation increases GDNF 
      production through FGFR/ERK signaling pathway. The current results indicate a 
      critical role of Gi/o signaling in the regulation of GDNF expression in 
      astrocytes.
FAU - Hisaoka-Nakashima, Kazue
AU  - Hisaoka-Nakashima K
AD  - Department of Pharmacology, Graduate School of Biomedical & Health Sciences, 
      Hiroshima University.
FAU - Matsumoto, Chie
AU  - Matsumoto C
AD  - Department of Pharmacology, Graduate School of Biomedical & Health Sciences, 
      Hiroshima University.
FAU - Azuma, Honami
AU  - Azuma H
AD  - Department of Pharmacology, Graduate School of Biomedical & Health Sciences, 
      Hiroshima University.
FAU - Taki, Sayaka
AU  - Taki S
AD  - Department of Pharmacology, Graduate School of Biomedical & Health Sciences, 
      Hiroshima University.
FAU - Takebayashi, Minoru
AU  - Takebayashi M
AD  - Division of Psychiatry and Neuroscience, Institute for Clinical Research, 
      National Hospital Organization (NHO) Kure Medical Center and Chugoku Cancer 
      Center.
AD  - Department of Psychiatry, National Hospital Organization (NHO) Kure Medical 
      Center and Chugoku Cancer Center.
FAU - Nakata, Yoshihiro
AU  - Nakata Y
AD  - Department of Pharmacology, Graduate School of Biomedical & Health Sciences, 
      Hiroshima University.
FAU - Morioka, Norimitsu
AU  - Morioka N
AD  - Department of Pharmacology, Graduate School of Biomedical & Health Sciences, 
      Hiroshima University.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Gdnf protein, rat)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Fibroblast Growth Factor)
RN  - 0 (Wasp Venoms)
RN  - 4091-50-3 (p-Methoxy-N-methylphenethylamine)
RN  - 72093-21-1 (mastoparan)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/*metabolism
MH  - Cells, Cultured
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - GTP-Binding Protein alpha Subunits, Gi-Go/*metabolism
MH  - Glial Cell Line-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Intercellular Signaling Peptides and Proteins
MH  - Peptides/pharmacology
MH  - Rats, Wistar
MH  - Receptors, Fibroblast Growth Factor/*metabolism
MH  - Wasp Venoms/pharmacology
MH  - p-Methoxy-N-methylphenethylamine/pharmacology
OTO - NOTNLM
OT  - Gi/o protein
OT  - astrocyte
OT  - brain-derived neurotrophic factor
OT  - glial cell line-derived neurotrophic factor
OT  - neurodegenerative disorder
OT  - neuropsychiatric disorder
EDAT- 2017/10/03 06:00
MHDA- 2018/06/13 06:00
CRDT- 2017/10/03 06:00
PHST- 2017/10/03 06:00 [entrez]
PHST- 2017/10/03 06:00 [pubmed]
PHST- 2018/06/13 06:00 [medline]
AID - 10.1248/bpb.b17-00383 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2017;40(10):1759-1766. doi: 10.1248/bpb.b17-00383.