Key resources table.

Reagent type (species) or resource	Designation	Source or reference	Identifiers	Additional information
Gene (H. sapiens)	MRGPRX4	hORFeome Database	Genbank Accession: KJ900052
Gene (H. sapiens)	TGR5	hORFeome Database	Genbank Accession: KJ895655
Cell line (Homo-sapiens)	HEK stable cell line for TGFα shedding assay	PMID: 22983457		Self-generated according to reference paper
Chemical compound, drug	Screen Quest Fluo-8 No Wash Calcium Assay Kit	AAT Bioquest	Cat. #: 36316
Chemical compound, drug	Fluo-8, AM	AAT Bioquest	Cat. #: 21083
Chemical compound, drug	Deoxycholic acid	Sigma-Aldrich	Cat. #: D2510
Chemical compound, drug	U73122	Selleck	Cat. #: S8011
Chemical compound, drug	Nateglinide	J and K Scientific	Cat. #: 586681
Chemical compound, drug	Bilirubin ditaurate	J and K Scientific	Cat. #: F-H130
Chemical compound, drug	Compound 15	custom- synthesized		Verified by HPLC and mass spectrum
Chemical compound, drug	Histamine	Sigma-Aldrich	Cat. #: H7250
Antibody	Rabbit polyclonal anti-hMRGPRX4	Abcam	Cat #: ab120808	IHC (1:200)
Antibody	Rabbit polyclonal anti-hTGR5	Thermofisher	Cat #: PA5-27076 RRID:AB_2544552	IHC (1:200-1:500)
Antibody	Mouse monoclonal anti-NeuN (clone A60)	Sigma-Aldrich	Cat. #: MAB377 RRID:AB_2298772	IHC (1:1000)
Antibody	Rabbit polyclonal anti-c-Myc	Sigma-Aldrich	Cat. #: C3956 RRID: AB_439680	IHC (1:200) FACS (1:50)
Antibody	Sheep polyclonal anti-Digoxigenin-AP	Roche	Cat. #: 11093274910 RRID:AB_2734716	ISH (1:1000)
Commercial assay or kit	RNAscope Fluorescent Multiplex Assay	Advanced Cell Diagnostics	Cat. #: 320293 UM
Commercial assay or kit	P3 Primary Cell 4D-NucleofectorTM X Kit L	Lonza	Cat. # V4XP-3012
Recombinant DNA reagent	pPiggyBac-MRGPRX4-P2A-mCherry (Plasmid)	This paper		See in Figure 1—figure supplement 1a
Recombinant DNA reagent	pPiggyBac-TGR5-P2A-mCherry (Plasmid)	This paper		See in Figure 1—figure supplement 1a
Other	Doxepin hydrochloride cream	Chongqing Huapont Pharm. Co.
Other	Cold cream	Eau Thermale Avène