PMID- 33327824
OWN - NLM
STAT- MEDLINE
DCOM- 20210923
LR  - 20210923
IS  - 1532-2513 (Electronic)
IS  - 0892-3973 (Linking)
VI  - 43
IP  - 1
DP  - 2021 Feb
TI  - MRGPRX2 is critical for clozapine induced pseudo-allergic reactions.
PG  - 77-84
LID - 10.1080/08923973.2020.1861006 [doi]
AB  - BACKGROUND: Clozapine is one of the most widely used second-generation 
      antipsychotics in clinic. However, allergy-like symptoms such as rash and 
      angioedema have been reported frequently, and the mechanism is still not clear. 
      Mas-related G protein-coupled receptor X2 (MRGPRX2) expressed on mast cells is a 
      crucial receptor for drug induced pseudo-allergic reactions. Therefore, we 
      explored whether the symptoms induced by clozapine were associated with allergic 
      reaction through MRGPRX2. METHODS: The effects of clozapine on pseudo-allergic 
      reactions were evaluated by mast cells degranulation and calcium mobilization 
      assay in vitro, and mice hindpaw swelling, serum histamine detection, avidin and 
      H&E staining assay in vivo. The overexpressed MRGPRX2 cells membrane 
      chromatography (MRGPRX2-HEK293/CMC), MRGPRX2-HEK293 cells calcium mobilization 
      assay and molecular docking were applied to research the correlation between 
      clozapine and MRGPRX2. RESULTS: The study showed that clozapine induced the 
      release of beta-hexosaminidase, histamine and monocyte chemoattractant protein-1 
      (MCP-1), and trigged calcium mobilization in mast cells. In vivo, clozapine 
      induced paw swelling, degranulation and vasodilation. Furthermore, clozapine 
      could activate the calcium mobilization obviously in MRGPRX2-HEK293 cells, not in 
      NC-HEK293 cells. Clozapine also had a good retention characteristic on 
      MRGPRX2-HEK293/CMC column and the K (D) value is (2.33 +/- 0.21)x10(-01)M. 
      CONCLUSIONS: Our findings demonstrated that clozapine could induce 
      pseudo-allergic reactions and MRGPRX2 might be the critical receptor for it.
FAU - Wei, Di
AU  - Wei D
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Hu, Tian
AU  - Hu T
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Hou, Ya-Jing
AU  - Hou YJ
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Wang, Xiang-Jun
AU  - Wang XJ
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Lu, Jia-Yu
AU  - Lu JY
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Ge, Shuai
AU  - Ge S
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - Wang, Cheng
AU  - Wang C
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
FAU - He, Huai-Zhen
AU  - He HZ
AD  - School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
LA  - eng
PT  - Journal Article
DEP - 20201217
PL  - England
TA  - Immunopharmacol Immunotoxicol
JT  - Immunopharmacology and immunotoxicology
JID - 8800150
RN  - 0 (MRGPRX2 protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Neuropeptide)
RN  - 0 (Serotonin Antagonists)
RN  - J60AR2IKIC (Clozapine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Cell Degranulation/*drug effects/physiology
MH  - Clozapine/*adverse effects/*metabolism
MH  - Drug Hypersensitivity/*metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nerve Tissue Proteins/*metabolism
MH  - Receptors, G-Protein-Coupled/*metabolism
MH  - Receptors, Neuropeptide/*metabolism
MH  - Serotonin Antagonists/adverse effects/metabolism
OTO - NOTNLM
OT  - Clozapine
OT  - MRGPRX2
OT  - calcium mobilization
OT  - degranulation
OT  - pseudo-allergic reactions
EDAT- 2020/12/18 06:00
MHDA- 2021/09/24 06:00
CRDT- 2020/12/17 05:29
PHST- 2020/12/18 06:00 [pubmed]
PHST- 2021/09/24 06:00 [medline]
PHST- 2020/12/17 05:29 [entrez]
AID - 10.1080/08923973.2020.1861006 [doi]
PST - ppublish
SO  - Immunopharmacol Immunotoxicol. 2021 Feb;43(1):77-84. doi: 
      10.1080/08923973.2020.1861006. Epub 2020 Dec 17.