PMID- 29311938
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 8
DP  - 2017
TI  - Prostaglandin E(2) Impairs P2Y(2)/P2Y(4) Receptor Signaling in Cerebellar 
      Astrocytes via EP3 Receptors.
PG  - 937
LID - 10.3389/fphar.2017.00937 [doi]
LID - 937
AB  - Prostaglandin E(2) (PGE(2)) is an important bioactive lipid that accumulates 
      after tissue damage or inflammation due to the rapid expression of cyclooxygenase 
      2. PGE(2) activates specific G-protein coupled EP receptors and it mediates pro- 
      or anti-inflammatory actions depending on the cell-context. Nucleotides can also 
      be released in these situations and they even contribute to PGE(2) production. We 
      previously described the selective impairment of P2Y nucleotide signaling by 
      PGE(2) in macrophages and fibroblasts, an effect independent of prostaglandin 
      receptors but that involved protein kinase C (PKC) and protein kinase D (PKD) 
      activation. Considering that macrophages and fibroblasts influence inflammatory 
      responses and tissue remodeling, a similar mechanism involving P2Y signaling 
      could occur in astrocytes in response to neuroinflammation and brain repair. We 
      analyzed here the modulation of cellular responses involving P2Y(2)/P2Y(4) 
      receptors by PGE(2) in rat cerebellar astrocytes. We demonstrate that PGE(2) 
      inhibits intracellular calcium responses elicited by UTP in individual cells and 
      that inhibiting this P2Y signaling impairs the astrocyte migration elicited by 
      this nucleotide. Activation of EP3 receptors by PGE(2) not only impairs the 
      calcium responses but also, the extracellular regulated kinases (ERK) and Akt 
      phosphorylation induced by UTP. However, PGE(2) requires epidermal growth factor 
      receptor (EGFR) transactivation in order to dampen P2Y signaling. In addition, 
      these effects of PGE(2) also occur in a pro-inflammatory context, as evident in 
      astrocytes stimulated with bacterial lipopolysaccharide (LPS). While we continue 
      to investigate the intracellular mechanisms responsible for the inhibition of UTP 
      responses, the involvement of novel PKC and PKD in cerebellar astrocytes cannot 
      be excluded, kinases that could promote the internalization of P2Y receptors in 
      fibroblasts.
FAU - Paniagua-Herranz, Lucia
AU  - Paniagua-Herranz L
AD  - Departamento de Bioquimica y Biologia Molecular IV, Facultad de Veterinaria, 
      Instituto Universitario de Investigacion en Neuroquimica, Instituto de 
      Investigacion Sanitaria del Hospital Clinico San Carlos, Universidad Complutense 
      Madrid, Madrid, Spain.
FAU - Gil-Redondo, Juan C
AU  - Gil-Redondo JC
AD  - Departamento de Bioquimica y Biologia Molecular IV, Facultad de Veterinaria, 
      Instituto Universitario de Investigacion en Neuroquimica, Instituto de 
      Investigacion Sanitaria del Hospital Clinico San Carlos, Universidad Complutense 
      Madrid, Madrid, Spain.
FAU - Queipo, Ma Jose
AU  - Queipo MJ
AD  - Departamento de Bioquimica y Biologia Molecular IV, Facultad de Veterinaria, 
      Instituto Universitario de Investigacion en Neuroquimica, Instituto de 
      Investigacion Sanitaria del Hospital Clinico San Carlos, Universidad Complutense 
      Madrid, Madrid, Spain.
FAU - Gonzalez-Ramos, Silvia
AU  - Gonzalez-Ramos S
AD  - Departamento de Bioquimica y Biologia Molecular IV, Facultad de Veterinaria, 
      Instituto Universitario de Investigacion en Neuroquimica, Instituto de 
      Investigacion Sanitaria del Hospital Clinico San Carlos, Universidad Complutense 
      Madrid, Madrid, Spain.
FAU - Bosca, Lisardo
AU  - Bosca L
AD  - Departamento de Bioquimica y Biologia Molecular IV, Facultad de Veterinaria, 
      Instituto Universitario de Investigacion en Neuroquimica, Instituto de 
      Investigacion Sanitaria del Hospital Clinico San Carlos, Universidad Complutense 
      Madrid, Madrid, Spain.
FAU - Perez-Sen, Raquel
AU  - Perez-Sen R
AD  - Departamento de Bioquimica y Biologia Molecular IV, Facultad de Veterinaria, 
      Instituto Universitario de Investigacion en Neuroquimica, Instituto de 
      Investigacion Sanitaria del Hospital Clinico San Carlos, Universidad Complutense 
      Madrid, Madrid, Spain.
FAU - Miras-Portugal, Ma Teresa
AU  - Miras-Portugal MT
AD  - Departamento de Bioquimica y Biologia Molecular IV, Facultad de Veterinaria, 
      Instituto Universitario de Investigacion en Neuroquimica, Instituto de 
      Investigacion Sanitaria del Hospital Clinico San Carlos, Universidad Complutense 
      Madrid, Madrid, Spain.
FAU - Delicado, Esmerilda G
AU  - Delicado EG
AD  - Departamento de Bioquimica y Biologia Molecular IV, Facultad de Veterinaria, 
      Instituto Universitario de Investigacion en Neuroquimica, Instituto de 
      Investigacion Sanitaria del Hospital Clinico San Carlos, Universidad Complutense 
      Madrid, Madrid, Spain.
LA  - eng
PT  - Journal Article
DEP - 20171222
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC5743739
OTO - NOTNLM
OT  - EP receptors
OT  - P2Y receptors
OT  - PGE2
OT  - astrocytes
OT  - calcium
OT  - nucleotide receptor
EDAT- 2018/01/10 06:00
MHDA- 2018/01/10 06:01
PMCR- 2017/12/22
CRDT- 2018/01/10 06:00
PHST- 2017/10/16 00:00 [received]
PHST- 2017/12/11 00:00 [accepted]
PHST- 2018/01/10 06:00 [entrez]
PHST- 2018/01/10 06:00 [pubmed]
PHST- 2018/01/10 06:01 [medline]
PHST- 2017/12/22 00:00 [pmc-release]
AID - 10.3389/fphar.2017.00937 [doi]
PST - epublish
SO  - Front Pharmacol. 2017 Dec 22;8:937. doi: 10.3389/fphar.2017.00937. eCollection 
      2017.