Phosphatidylethanolamine‑binding protein is not involved in µ‑opioid receptor-mediated regulation of extracellular signal‑regulated kinase

Bian,Jia‑Ming; Wu,Ning; Su,Rui‑Bin; Li,Jin

doi:10.3892/mmr.2015.3161

Phosphatidylethanolamine‑binding protein is not involved in µ‑opioid receptor-mediated regulation of extracellular signal‑regulated kinase

Authors:
- Jia‑Ming Bian
- Ning Wu
- Rui‑Bin Su
- Jin Li
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Affiliations: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P.R. China
Published online on: January 8, 2015 https://doi.org/10.3892/mmr.2015.3161
Pages: 3368-3374
Copyright: © Bian et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Stimulation of the µ‑opioid receptor activates extracellular signal‑regulated kinase (ERK), however, the mechanism by which this occurs remains to be elucidated. Phosphatidylethanolamine‑binding protein (PEBP) has been reported to act as a negative regulator of the ERK cascade (Raf‑MEK‑ERK) by binding to Raf‑1 kinase. In the present study, the role of PEBP in µ‑opioid receptor‑mediated ERK activation was investigated in Chinese hamster ovary/µ cells and SH‑SY5Y cells, as well as in human embryonic kidney 293 cells expressing other types of G protein‑coupled receptors. The acute activation of µ‑opioid receptors by morphine or (D‑Ala2, MePhe4, Gly5‑ol) enkephalin induced a rapid activation of ERK. Prolonged morphine treatment did not affect the phosphorylation level of ERK compared with control cells, but the phosphorylation level of ERK decreased markedly when cells were precipitated with naloxone following chronic morphine treatment. For the phosphorylation of PEBP, no change was identified under the designated drug treatment and exposure duration. A total of two other types of G protein‑coupled receptors, including Gs‑coupled dopamine D1 receptors and Gq‑coupled adrenergic α1A receptors were also investigated and only the activation of adrenergic α1A receptors induced an upregulated phosphorylation of PEBP, which was protein kinase C activity dependent. Thus, PEBP did not have a significant role in µ‑opioid receptor‑mediated regulation of ERK.

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