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J Pharm Pharmacol. 2018 Dec;70(12):1596-1605. doi: 10.1111/jphp.13009. Epub 2018 Sep 6.

Relationship between MRGPRX2 and pethidine hydrochloride- or fentanyl citrate-induced LAD2 cell degranulation.

Author information

1
School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.

Abstract

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 β-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)-α, interleukin (IL)-8, monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein (MIP-1β) 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.

KEYWORDS:

MRGPRX2; degranulation; fentanyl; mast cells; pethidine

PMID:
30256417
DOI:
10.1111/jphp.13009
[Indexed for MEDLINE]

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