Endogenous δ-opioid and ORL1 receptors couple to phosphorylation and activation of p38 MAPK in NG108-15 cells and this is regulated by protein kinase A and protein kinase C

Zhe Zhang, Shun Mei Xin, Guo Xiang Wu, Wenbo Zhang, Lan Ma, Gang Pei

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The p38 mitogen-activated protein kinase (MAPK) cascade transduces multiple extracellular signals from cell surface to nucleus and is employed in cellular responses to cellular stresses and apoptotic regulation. The involvement of the p38 MAPK cascade in opioid- and opioid receptor-like receptor-1 (ORL1) receptor-mediated signal transduction was examined in NG108-15 neuroblastoma x glioma hybrid cells. Stimulation of endogenous δ- opioid receptor (DOR) or ORL1 resulted in activation of p38 MAPK. It also reduced the activation of extracellular signal-regulated kinases (ERKs), another member of the MAPK family, with slower kinetics. Activation of p38 MAPK was abolished by selective antagonists of DOR or ORL1, pretreatment with pertussis toxin, or SB203580, a specific inhibitor of p38 MAPK. Inhibition of p38 MAPK had no significant effect on opioid-induced ERK activation, indicating that p38 MAPK activity was not required for ERK activation, though its stimulation preceded ERK activation. Inhibition of protein kinase A (PKA) strongly diminished p38 activation mediated by DOR or ORL1 but had no significant effect on ERK activation, and protein kinase C (PKC) inhibitors potentiated stimulation of p38 while inhibiting activation of ERKs. Taken together, our results provide the first evidence for coupling of DOR and ORL1 to the p38 MAPK cascade and clearly demonstrate that receptor-mediated activation of p38 MAPK both revolves PKA and is negatively regulated by PKC.

Original languageEnglish (US)
Pages (from-to)1502-1509
Number of pages8
JournalJournal of Neurochemistry
Volume73
Issue number4
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Phosphorylation
Opioid Receptors
p38 Mitogen-Activated Protein Kinases
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C
Opioid Analgesics
Chemical activation
Extracellular Signal-Regulated MAP Kinases
Protein C Inhibitor
Hybrid Cells
Signal transduction
Pertussis Toxin
Protein Kinase Inhibitors
Mitogen-Activated Protein Kinases
Neuroblastoma
Glioma
Signal Transduction
Thermodynamic properties

Keywords

  • G protein
  • Opioid receptor
  • p38 mitogen-activated protein kinase
  • Protein kinase A
  • Protein kinase C

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Endogenous δ-opioid and ORL1 receptors couple to phosphorylation and activation of p38 MAPK in NG108-15 cells and this is regulated by protein kinase A and protein kinase C. / Zhang, Zhe; Xin, Shun Mei; Wu, Guo Xiang; Zhang, Wenbo; Ma, Lan; Pei, Gang.

In: Journal of Neurochemistry, Vol. 73, No. 4, 1999, p. 1502-1509.

Research output: Contribution to journalArticle

@article{25cc5395f382417091f510a0f0b9313b,
title = "Endogenous δ-opioid and ORL1 receptors couple to phosphorylation and activation of p38 MAPK in NG108-15 cells and this is regulated by protein kinase A and protein kinase C",
abstract = "The p38 mitogen-activated protein kinase (MAPK) cascade transduces multiple extracellular signals from cell surface to nucleus and is employed in cellular responses to cellular stresses and apoptotic regulation. The involvement of the p38 MAPK cascade in opioid- and opioid receptor-like receptor-1 (ORL1) receptor-mediated signal transduction was examined in NG108-15 neuroblastoma x glioma hybrid cells. Stimulation of endogenous δ- opioid receptor (DOR) or ORL1 resulted in activation of p38 MAPK. It also reduced the activation of extracellular signal-regulated kinases (ERKs), another member of the MAPK family, with slower kinetics. Activation of p38 MAPK was abolished by selective antagonists of DOR or ORL1, pretreatment with pertussis toxin, or SB203580, a specific inhibitor of p38 MAPK. Inhibition of p38 MAPK had no significant effect on opioid-induced ERK activation, indicating that p38 MAPK activity was not required for ERK activation, though its stimulation preceded ERK activation. Inhibition of protein kinase A (PKA) strongly diminished p38 activation mediated by DOR or ORL1 but had no significant effect on ERK activation, and protein kinase C (PKC) inhibitors potentiated stimulation of p38 while inhibiting activation of ERKs. Taken together, our results provide the first evidence for coupling of DOR and ORL1 to the p38 MAPK cascade and clearly demonstrate that receptor-mediated activation of p38 MAPK both revolves PKA and is negatively regulated by PKC.",
keywords = "G protein, Opioid receptor, p38 mitogen-activated protein kinase, Protein kinase A, Protein kinase C",
author = "Zhe Zhang and Xin, {Shun Mei} and Wu, {Guo Xiang} and Wenbo Zhang and Lan Ma and Gang Pei",
year = "1999",
doi = "10.1046/j.1471-4159.1999.0731502.x",
language = "English (US)",
volume = "73",
pages = "1502--1509",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Endogenous δ-opioid and ORL1 receptors couple to phosphorylation and activation of p38 MAPK in NG108-15 cells and this is regulated by protein kinase A and protein kinase C

AU - Zhang, Zhe

AU - Xin, Shun Mei

AU - Wu, Guo Xiang

AU - Zhang, Wenbo

AU - Ma, Lan

AU - Pei, Gang

PY - 1999

Y1 - 1999

N2 - The p38 mitogen-activated protein kinase (MAPK) cascade transduces multiple extracellular signals from cell surface to nucleus and is employed in cellular responses to cellular stresses and apoptotic regulation. The involvement of the p38 MAPK cascade in opioid- and opioid receptor-like receptor-1 (ORL1) receptor-mediated signal transduction was examined in NG108-15 neuroblastoma x glioma hybrid cells. Stimulation of endogenous δ- opioid receptor (DOR) or ORL1 resulted in activation of p38 MAPK. It also reduced the activation of extracellular signal-regulated kinases (ERKs), another member of the MAPK family, with slower kinetics. Activation of p38 MAPK was abolished by selective antagonists of DOR or ORL1, pretreatment with pertussis toxin, or SB203580, a specific inhibitor of p38 MAPK. Inhibition of p38 MAPK had no significant effect on opioid-induced ERK activation, indicating that p38 MAPK activity was not required for ERK activation, though its stimulation preceded ERK activation. Inhibition of protein kinase A (PKA) strongly diminished p38 activation mediated by DOR or ORL1 but had no significant effect on ERK activation, and protein kinase C (PKC) inhibitors potentiated stimulation of p38 while inhibiting activation of ERKs. Taken together, our results provide the first evidence for coupling of DOR and ORL1 to the p38 MAPK cascade and clearly demonstrate that receptor-mediated activation of p38 MAPK both revolves PKA and is negatively regulated by PKC.

AB - The p38 mitogen-activated protein kinase (MAPK) cascade transduces multiple extracellular signals from cell surface to nucleus and is employed in cellular responses to cellular stresses and apoptotic regulation. The involvement of the p38 MAPK cascade in opioid- and opioid receptor-like receptor-1 (ORL1) receptor-mediated signal transduction was examined in NG108-15 neuroblastoma x glioma hybrid cells. Stimulation of endogenous δ- opioid receptor (DOR) or ORL1 resulted in activation of p38 MAPK. It also reduced the activation of extracellular signal-regulated kinases (ERKs), another member of the MAPK family, with slower kinetics. Activation of p38 MAPK was abolished by selective antagonists of DOR or ORL1, pretreatment with pertussis toxin, or SB203580, a specific inhibitor of p38 MAPK. Inhibition of p38 MAPK had no significant effect on opioid-induced ERK activation, indicating that p38 MAPK activity was not required for ERK activation, though its stimulation preceded ERK activation. Inhibition of protein kinase A (PKA) strongly diminished p38 activation mediated by DOR or ORL1 but had no significant effect on ERK activation, and protein kinase C (PKC) inhibitors potentiated stimulation of p38 while inhibiting activation of ERKs. Taken together, our results provide the first evidence for coupling of DOR and ORL1 to the p38 MAPK cascade and clearly demonstrate that receptor-mediated activation of p38 MAPK both revolves PKA and is negatively regulated by PKC.

KW - G protein

KW - Opioid receptor

KW - p38 mitogen-activated protein kinase

KW - Protein kinase A

KW - Protein kinase C

UR - http://www.scopus.com/inward/record.url?scp=0032872188&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032872188&partnerID=8YFLogxK

U2 - 10.1046/j.1471-4159.1999.0731502.x

DO - 10.1046/j.1471-4159.1999.0731502.x

M3 - Article

C2 - 10501195

AN - SCOPUS:0032872188

VL - 73

SP - 1502

EP - 1509

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 4

ER -