In:
Journal of Pharmacy and Pharmacology, Oxford University Press (OUP), Vol. 70, No. 12 ( 2018-11-08), p. 1596-1605
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0022-3573
,
2042-7158
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2018
detail.hit.zdb_id:
2041988-0
detail.hit.zdb_id:
2050532-2
SSG:
15,3
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