. 2021 Apr 27;10(5):1033. doi: 10.3390/cells10051033

Table 1.

Summary of the MRGPRX2/MRGPRB2 agonists (peptides, non-peptides and natural compounds).

SN	Agonist	Major Findings	References
Peptide Agonist
1	CST-14	MRGPRX2-dependent MC activation, degranulation and cytokine release Increased Ca²⁺ mobilization Involvement of store-operated Ca²⁺ entry via stim1	[72,75,104]
2	Substance P	Presence of MRGPRs in primary sensory neurons and on nerve endings of dorsal root ganglion MRGPRX2-dependent activation of human skin-derived cultured MCs MRGPRX2-dependent itch response	[46,67,70]
3	Somatostatin	MRGPRX2-dependent MC degranulation	[45,73]
4	PACAP	MRGPRX2-dependent MC degranulation	[45]
5	VIP	MRGPRX2-dependent MC degranulation	[45]
6	LL-37	MRGPRX2-dependent LL-37 induces MC degranulation, chemokine generation, and chemotaxis Increased Ca²⁺ mobilization	[50,103]
7	β-defensins	Identification of MRGPRX2 in human β-defensin-induced MC degranulation Increased vascular permeability in rats	[103]
8	Indolicidin	Increased Ca²⁺ influx in MRGPRX2-expressing cells Dose-dependent degranulation of human MCs	[45]
9	PAMP 20	Identified as an endogenous ligand for MRGPRX2 Similar binding site as of Cortistatin	[75,105]
10	Mastoparan	Concentration-dependent MRGPRX2 activation Concentration-dependent MC degranulation and inflammatory mediators release activity	[72,91]
11	Human eosinophil granules	MRGPRX2-dependent activation of human MCs Identified major basic protein-1 (MBP-1) and major basic protein-2 (MBP-2), eosinophil peroxidase (EPO) and eosinophil cationic protein (ECP) as MRGPRX2 agonists	[45,46,106]
12	Proteases	Identified cysteine endopeptidase cathepsin S and mucunain allergic response via MRGPRX2 MRGPRX2-dependent chronic inflammation and itch response	[107,108]
13	AG-30/5C	Identified AG-30/5C as biased MRGPRX2 agonist Induction of chemotaxis and cytokine production via MRGPRX2-mediated MC activation	[95]
14	AMP-IBP5	Identified AMP-IBP5 as MRGPRX2 agonist Role in wound healing through MCs–MRGPRX2 AMP-IBP5 shown Ca²⁺ flux followed by MC degranulation and release PGDs, and cytokines/chemokines.	[48]
15	GnRHR agonist and antagonist	Sermorelin and octreotide as MRGPRX2 agonist Increased Ca²⁺ mobilization in MRGPRX2-transfected cells	[72]
Non-peptide agonist
1	Compound 48/80	MRGPRX2-dependent MC activation of different population of MCs Increased Ca²⁺ mobilization, and cytokine release	[45,72,109]
2	Fluoroquinolone antibiotics (ciprofloxacin)	MRGPRX2-dependent hypersensitivity reaction by topical fluoroquinolone ophthalmic preparation Concentration-dependent MC degranulation, and MRGPRX2-dependent Ca²⁺ release by ciprofloxacin Dose dependent MC degranulation, Ca²⁺ release and increased vascular permeability	[72,110,111]
3	NMBAs (rocuronium, mivacurium, and atracurium)	Rocuronium-induced non-IgE-mediated allergic reaction clinically Concentration-dependent MCs–MRGPRX2/MRGPRB2 by rocuronium MC Ca²⁺ mobilization and degranulation concentration-dependent activation of MRGPRX2, MC degranulation, histamine and inflammatory cytokine release by mivacurium Increased paw extravasation and decreased body temperature by mivacurium	[72,85,112]
4	Opioids (morphine, pethidine chloride, dextrorphan, levorphanol)	MRGPRX2-mediated MC activation and intrathecal mass formation. Concentration-dependent MRGPRX2 activation and MC activity of morphine Dextro-enantiomers and N-methyl scaffolds of opioids and endogenous opioid ligands activates MCs via MRGPRX2 Increased Ca²⁺ mobilization and MC degranulation activity Concentration-dependent human MC degranulation and inflammatory cytokine release by pethidine hydrocholoride	[87,113,114]
5	Antidepressant drugs (clomipramine paroxetine and desipramine	Concentration-dependent activation of MRGPRX2/MRGPRB2 and MC activation Induced scratch behavior in mice Clomipramine showed wheal-and-flare reaction on intradermal injection and activated human skin MCs	[115]
6	Others (Icatibant, iopamidol, vancomycin, baicalein, and sinomemnin)	MRGPRX2/MRGPRB2 activation MC degranulation and Ca²⁺ mobilization Induced tissue extravasation and cytokine release	[72,92,95,116]