TABLE 1.

A summary of roles of neurotransmitters receptors in the pathological mechanism of digestive diseases.

Neurotransmitters receptors	Target cells	Related diseases	Biological effect	Authors/References
5-HT
5- -HT1D, 5-HT2B	HCC cells	HCC	• Promotes the viability and proliferation of HCC • Promotes hepatocarcinogenesis	Liang et al., 2013; Niture et al., 2018; Zuo et al., 2019
5-HT2A, 5-HT2B	HSCs	Hepatic fibrosis	• Promotes HSCs proliferation, transcription	Ruddell et al., 2006; Ebrahimkhani et al., 2011; Kim D. C. et al., 2013
5-HT3		IBS	• Relieves abdominal pain, inhibits hypermotility	Salaga et al., 2018
5-HT4	Esophage	Reflux esophagitis and non-erosive reflux disease	• Relates with the contraction of the lower esophageal muscle	Yang et al., 2012
	Colonic epithelium	IBD	• Maintains motility • Reduces inflammation	Spohn et al., 2016
		IBS	• Inhibits visceral hypersensitivity	Hoffman et al., 2012; Gilet et al., 2014
5-HT7	GI epithelial cells	Infective acute enteritis, colitis, IBD	• Pro-inflammation	Kim J. J. et al., 2013
			• Anti-inflammation	Guseva et al., 2014
Catecholamines
DRD1	Gastrointestinal mucosa	Stress-induced gastric ulcers	• Reduces the incidence of gastric and duodenal ulcers	Rasheed et al., 2010
	iNKT cells	Autoimmune hepatitis	• Suppress iNKT cell-mediated hepatitis	Xue et al., 2018
DRD2	Pancreatic acinar cells	AP	• Controls inflammation. • Reduces pancreatic damage	Han et al., 2017, 2020
	Pancreatic ductal adenocarcinoma cells	Pancreatic ductal adenocarcinoma	• Promotes proliferation of pancreatic cancer cells	Jandaghi et al., 2016
	Gastric tumor endothelial cells	GC	• Suppresses gastric cancer cell proliferation, invasion and migration	Chakroborty et al., 2004; Ganguly et al., 2010; Huang et al., 2016
	HCC cells	HCC	• Suppresses liver cancer cells proliferation migration and invasion • Reduces EMT, inhibits liver tumor growth	Li et al., 2015; Liu et al., 2017
ADRB2	BM-DMs	Colitis	• Suppress inflammation	Agac et al., 2018
	Gastric cancer cells	GC	• Promotes gastric cancer progression, metastasis, angiogenesis • Induces autophagy	Lu et al., 2017; Zhang et al., 2019; Zhi et al., 2019
	Pancreatic cancer cells	Pancreatic cancer	• Accelerates pancreatic cancer growth and invasion • Promotes angiogenesis and metastasis of pancreatic cancer	Hu et al., 2010; Kim-Fuchs et al., 2014
	HCC cells	HCC	l lPromotes HCC progression	Wu et al., 2016
ADRA1	HSCs	Hepatic fibrosis	• Promotes HSCs activation, proliferation and secretion of ECM	Sancho-Bru et al., 2006; Liu et al., 2014
	KCs, HCC cells	HCC	• Boosts the activation of KCs and to maintain the inflammatory microenvironment	Han et al., 2008; Huan et al., 2017
ADRA2	HCC cells	Hepatocellular dysfunction in early sepsis	• Induces hepatocellular dysfunction	Yang et al., 2001
Glutamate receptors
iGluR
AMPA	Colon endothelial cells	Colitis	• Enhance the efficiency of peristalsis	Giaroni et al., 2000
	Pancreatic cancer cells	Pancreatic cancer	• Increased invasion and migration	Herner et al., 2011
NMDA	Colon endothelial cells	Ulcerative colitis	• Promoted colon motility and inflammation	Erces et al., 2012; Motaghi et al., 2016
	Colon endothelial cells	GI diseases	• Induced proinflammatory neuropeptides, calcitonin gene-related peptide and substance • Increased colonic anaphylaxis	Cao et al., 2008; Fan et al., 2009
	Gastric epithelial cell	GC	• Resulted in Ca2+ permeation and epithelial cell death	Seo et al., 2011
	Colon adenocarcinoma cells	Colon adenocarcinoma	• Limited tumor growth	Rzeski et al., 2001
	Kupffer cells	Hepatitis	• Limited inflammasome and injury	Farooq et al., 2014
		Pancreatic neuroendocrine tumor	• Controlled invasion of tumor
mGluR
mGluR5	Esophage epithelial cell	GERD	• Triggered TLESRs and gastroesophageal reflux	Frisby et al., 2005
		IBS, FD	• Promoted visceromotor and autonomic responses	Lindstrom et al., 2008
	HSCs	Hepatic fibrosis	• Stimulated 2-AG production	Choi et al., 2019
mGluR7	Colon mucosa	GI dysfunction	• Attenuated visceral hypersensitivity	Shao et al., 2019