PMID- 36257460
OWN - NLM
STAT- MEDLINE
DCOM- 20221130
LR  - 20221130
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 311
IP  - Pt A
DP  - 2022 Dec 15
TI  - Extracellular Ca(2+) aggravates IgE-induced allergic reaction in mast cells 
      through GPRC6A, a novel family C G-protein-coupled receptor.
PG  - 121013
LID - S0024-3205(22)00713-5 [pii]
LID - 10.1016/j.lfs.2022.121013 [doi]
AB  - AIMS: As an essential indicator of allergic reactions, mast cell (MC) activation 
      involves FcepsilonRI-mediated signaling and the release of allergic mediators. In FcepsilonRI 
      signaling, Ca(2+) is located at the intersection of multiple cellular signaling 
      pathways. However, the effect of extracellular Ca(2+) (exCa(2+)) on MCs during 
      anaphylaxis remains unclear, along with its exact mechanisms. Therefore, we 
      sought to determine whether and how elevated exCa(2+) amplifies allergic 
      reactions. MAIN METHODS: In vitro experiments used immunoglobulin E (IgE)/antigen 
      (Ag)-induced activation of rat and mouse MCs in vitro. The levels of MC 
      degranulation mediators were used to evaluate the effect of exCa(2+). In vivo 
      experiments used MC-mediated passive systemic anaphylaxis (PCA) Balb/c mice. 
      After stimulation, anaphylaxis indexes such as rectal temperature and allergic 
      symptom score were detected. KEY FINDINGS: In vitro experiments revealed that 
      exCa(2+) is a stimulus signal for the aggravation of allergic reactions in MCs. 
      When antagonists or siRNA inhibited GPRC6, MCs released fewer inflammatory 
      mediators. Moreover, in vivo experiments confirmed in vitro results. Allergic 
      symptoms were alleviated by antagonists NPS2143 in PCA mice, demonstrating that 
      exCa(2+) aggravates allergic reactions through GPRC6A. SIGNIFICANCE: Our study 
      provides an essential theoretical basis for targeting Ca(2+) and GPRC6A as 
      therapeutic options for allergies.
CI  - Copyright (c) 2022. Published by Elsevier Inc.
FAU - Liu, Guirong
AU  - Liu G
AD  - Beijing Advanced Innovation Center for Food Nutrition and Human Health, College 
      of Food Science and Nutritional Engineering, China Agricultural University, 
      Beijing 100083, PR China.
FAU - Han, Shiwen
AU  - Han S
AD  - Beijing Advanced Innovation Center for Food Nutrition and Human Health, College 
      of Food Science and Nutritional Engineering, China Agricultural University, 
      Beijing 100083, PR China.
FAU - Jiang, Songsong
AU  - Jiang S
AD  - College of Food Science and Technology, Yangzhou University, Yangzhou, Jiangsu 
      Province 225127, PR China.
FAU - Jiang, Yuchi
AU  - Jiang Y
AD  - Beijing Advanced Innovation Center for Food Nutrition and Human Health, College 
      of Food Science and Nutritional Engineering, China Agricultural University, 
      Beijing 100083, PR China.
FAU - Chen, Cheng
AU  - Chen C
AD  - Beijing Advanced Innovation Center for Food Nutrition and Human Health, College 
      of Food Science and Nutritional Engineering, China Agricultural University, 
      Beijing 100083, PR China.
FAU - Sun, Na
AU  - Sun N
AD  - School of Food Science and Technology, Dalian Polytechnic University, National 
      Engineering Research Center of Seafood, Dalian 116034, PR China.
FAU - Che, Huilian
AU  - Che H
AD  - Beijing Advanced Innovation Center for Food Nutrition and Human Health, College 
      of Food Science and Nutritional Engineering, China Agricultural University, 
      Beijing 100083, PR China; College of Food Science and Nutritional Engineering, 
      China Agricultural University, Beijing 100083, PR China. Electronic address: 
      chehuilian@cau.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20221017
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (GPRC6A protein, mouse)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Rats
MH  - *Anaphylaxis/metabolism
MH  - Cell Degranulation
MH  - Immunoglobulin E
MH  - *Mast Cells/immunology
MH  - Mice, Inbred BALB C
MH  - *Receptors, G-Protein-Coupled/metabolism
MH  - Signal Transduction
MH  - *Calcium/metabolism
OTO - NOTNLM
OT  - Allergic diseases
OT  - Extracellular calcium
OT  - G protein-coupled calcium sensing receptors
OT  - G protein-coupled receptor class C group 6 member A (GPRC6A)
OT  - Mast cells (MCs)
COIS- Declaration of competing interest The authors have no conflicts of interest to 
      disclose.
EDAT- 2022/10/19 06:00
MHDA- 2022/11/30 06:00
CRDT- 2022/10/18 19:24
PHST- 2022/07/28 00:00 [received]
PHST- 2022/09/17 00:00 [revised]
PHST- 2022/09/26 00:00 [accepted]
PHST- 2022/10/19 06:00 [pubmed]
PHST- 2022/11/30 06:00 [medline]
PHST- 2022/10/18 19:24 [entrez]
AID - S0024-3205(22)00713-5 [pii]
AID - 10.1016/j.lfs.2022.121013 [doi]
PST - ppublish
SO  - Life Sci. 2022 Dec 15;311(Pt A):121013. doi: 10.1016/j.lfs.2022.121013. Epub 2022 
      Oct 17.