PMID- 30256417
OWN - NLM
STAT- MEDLINE
DCOM- 20190225
LR  - 20190225
IS  - 2042-7158 (Electronic)
IS  - 0022-3573 (Linking)
VI  - 70
IP  - 12
DP  - 2018 Dec
TI  - Relationship between MRGPRX2 and pethidine hydrochloride- or fentanyl 
      citrate-induced LAD2 cell degranulation.
PG  - 1596-1605
LID - 10.1111/jphp.13009 [doi]
AB  - OBJECTIVES: Pethidine hydrochloride (PH) and fentanyl citrate (FC) are opioid 
      receptor agonists commonly used to treat pain clinically. PH and FC have been 
      reported to have a high potential for pseudoallergic effects, but the underlying 
      mechanism has not been well studied. MRGPRX2 is a novel atypical opioid receptor 
      that is mainly expressed in human mast cells and considered to mediate 
      drug-induced pseudoallergic reactions. This study aimed to investigate the 
      allergy effect of these two opioid receptor agonists and the possible association 
      of MRGPRX2 with this response. METHODS: HEK293-MRGPRX2/CMC assay, molecular 
      docking assay, calcium mobilization assay, the test of beta-hexosaminidase, 
      histamine and cytokine release assay were performed in this article. KEY 
      FINDINGS: PH but not FC induced LAD2 cell activation and degranulation 
      dose-dependently. Histamine, tumour necrosis factor (TNF)-alpha, interleukin (IL)-8, 
      monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein 
      (MIP-1beta) levels were upregulated by PH, but not FC. The PH-induced activation of 
      mast cell was MRGPRX2-dependent. CONCLUSIONS: PH but not FC activated mast cells, 
      leading to degranulation mediated via MRGPRX2 receptors, which could be greatly 
      significant in future clinical applications of opioid receptor drugs.
CI  - (c) 2018 Royal Pharmaceutical Society.
FAU - Liu, Rui
AU  - Liu R
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Wang, Jue
AU  - Wang J
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Zhao, Tingting
AU  - Zhao T
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Cao, Jiao
AU  - Cao J
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Che, Delu
AU  - Che D
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Ma, Pengyu
AU  - Ma P
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Zhang, Yongjing
AU  - Zhang Y
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Zhang, Tao
AU  - Zhang T
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Wang, Nan
AU  - Wang N
AUID- ORCID: 0000-0002-4197-4245
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
LA  - eng
GR  - 81230079/National Natural Science Foundation of China/
GR  - 81227802/National Natural Science Foundation of China/
GR  - 81503321/National Natural Science Foundation of China/
GR  - xjj2016125/Fundamental Research Funds for the Central University/
GR  - 15-ZY032/Shaanxi Administration of Traditional Chinese Medicine/
PT  - Journal Article
DEP - 20180906
PL  - England
TA  - J Pharm Pharmacol
JT  - The Journal of pharmacy and pharmacology
JID - 0376363
RN  - 0 (Cytokines)
RN  - 0 (Histamine Antagonists)
RN  - 0 (MRGPRX2 protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Neuropeptide)
RN  - 820484N8I3 (Histamine)
RN  - EC 3.2.1.52 (beta-N-Acetylhexosaminidases)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - UF599785JZ (Fentanyl)
SB  - IM
MH  - Cell Degranulation/*drug effects
MH  - Cytokines/biosynthesis
MH  - Dose-Response Relationship, Drug
MH  - Fentanyl/*pharmacology
MH  - HEK293 Cells
MH  - Histamine/metabolism
MH  - Histamine Antagonists/*pharmacology
MH  - Humans
MH  - Hypersensitivity/*drug therapy
MH  - Mast Cells/drug effects
MH  - Molecular Docking Simulation
MH  - Nerve Tissue Proteins
MH  - Peptide Hydrolases/drug effects
MH  - Receptors, G-Protein-Coupled
MH  - Receptors, Neuropeptide
MH  - Signal Transduction/drug effects
MH  - Up-Regulation
MH  - beta-N-Acetylhexosaminidases/biosynthesis
OTO - NOTNLM
OT  - MRGPRX2
OT  - degranulation
OT  - fentanyl
OT  - mast cells
OT  - pethidine
EDAT- 2018/09/27 06:00
MHDA- 2019/02/26 06:00
CRDT- 2018/09/27 06:00
PHST- 2018/06/13 00:00 [received]
PHST- 2018/08/10 00:00 [accepted]
PHST- 2018/09/27 06:00 [pubmed]
PHST- 2019/02/26 06:00 [medline]
PHST- 2018/09/27 06:00 [entrez]
AID - 10.1111/jphp.13009 [doi]
PST - ppublish
SO  - J Pharm Pharmacol. 2018 Dec;70(12):1596-1605. doi: 10.1111/jphp.13009. Epub 2018 
      Sep 6.