Stabilization of activated mast cells by ORAI1 inhibitor suppresses peanut-induced anaphylaxis and acute diarrhea

Gyeongseo Suk, Do Hoon Kwon, Axel Roers, Soman N. Abraham, Hae Woong Choi

Research output: Contribution to journalArticlepeer-review


Mast cell (MC) activation triggered by immunoglobulin E (IgE)-antigen crosslinking involves intracellular Ca2+ influx through the ORAI1 channel, which precedes granule exteriorization and de novo synthesis of mediators. Pharmacologically suppressing MCs via the inhibition of the ORAI1 Ca2+ channel may represent a potential strategy for preventing anaphylaxis. This study demonstrated that peanut-induced anaphylaxis in sensitized mice resulted in significant hypothermia and acute diarrhea. Utilizing the Mcpt5cre-DTA mouse model, we demonstrated that this anaphylactic response was mediated by IgE-antigen-induced MC activation. Prophylactic administration of MC suppressors was an effective means of preventing peanut-induced anaphylaxis. In addition, we observed the potent efficacy of an ORAI1 inhibitor in suppressing the FcεRI-mediated response of murine or human MCs, even when administered concurrently or post-allergen exposure. Mechanistically, the ORAI1 inhibitor was found to prevent the association of Synaptotagmin-2 with the SNARE complex. In an in vivo mouse model of peanut-induced anaphylaxis, the administration of the ORAI1 inhibitor after allergen challenge effectively suppressed allergic acute diarrhea and ameliorated anaphylaxis. Therefore, pharmacological intervention of ORAI1 channel inhibition in MCs represents a promising therapeutic avenue for the treatment of peanut-induced anaphylaxis and acute diarrhea in vivo.

Original languageEnglish
Article number106887
JournalPharmacological Research
Publication statusPublished - 2023 Oct

Bibliographical note

Publisher Copyright:
© 2023 The Authors


  • Allergy
  • Anaphylaxis
  • Mast cell
  • ORAI1 inhibitor

ASJC Scopus subject areas

  • Pharmacology


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