Table 1.

CaSR and modulations of digestive functions.

Cell types that express	Activating nutrient(s)	Role and function	Type of evidence	References
CELLS THAT REGULATE INGESTION AND DIGESTION
Tongue
Taste buds	${\text{Ca}}_{\text{o}}^{2+}$, γ-glutamyl peptide	↑bitter and kokumi taste perception	Pharmacological	Ohsu et al., 2010; Maruyama et al., 2012
Esophagus
Epithelial cells (basal cells)		Inflammation-modulating (?)	Biochemical	Justinich et al., 2008; Abdulnour-Nakhoul et al., 2015
Stomach
G cells (ap & bl)	${\text{Ca}}_{\text{o}}^{2+}$, Phe, spermine, Peptide, cinacalcet	↑gastrin ↑gastric H+ production	Pharmacogenetic	Ray et al., 1997; Buchan et al., 2001
D cells			Biochemical	Haid et al., 2012; Adriaenssens et al., 2015
Ghrelin cells (ap & bl)	Phe, Ala, peptide	↑and ↓ghrelin secretion	Pharmacological	Engelstoft et al., 2013; Vancleef et al., 2015
Parietal cells (bl)	${\text{Ca}}_{\text{o}}^{2+}$, Mg2+, amino acid	↑gastric H+ secretion	Biochemical	Cheng et al., 1999; Caroppo et al., 2001; Geibel et al., 2001; Busque et al., 2005; Dufner et al., 2005
Mucous cells (ap & bl)	${\text{Ca}}_{\text{o}}^{2+}$	↑mucous secretion	Biochemical	Rutten et al., 1999; Gilster et al., 2004
Duodenum
I cells (ap & bl)	${\text{Ca}}_{\text{o}}^{2+}$, Phe, Trp, peptide	↑CCK↑pancreatic juice & bile	Pharmacogenetic	Sheinin et al., 2000; Hira et al., 2008; Nakajima et al., 2010, 2012; Liou et al., 2011; Wang et al., 2011
Pancreas
Acinar cells		↑ secretion of pancreatic juice (?)	Biochemical	Bruce et al., 1999
Ductal cells (ap)	${\text{Ca}}_{\text{o}}^{2+}$	↑pancreatic fluid flow & solubility	Biochemical	Bruce et al., 1999
α & β cells of Islet	${\text{Ca}}_{\text{o}}^{2+}$, L-His	↑insulin↑nutrient utilization	Biochemical	Bruce et al., 1999; Squires et al., 2000; Komoto et al., 2003; Leech and Habener, 2003
Liver
Hepatocytes	${\text{Ca}}_{\text{o}}^{2+}$, spermine	↑bile flow	Biochemical	Canaff et al., 2001
Cholangiocytes (?)
CELLS THAT REGULATE ABSORPTION AND SECRETION
Small intestine
Villus cells (ap & bl)		↑absorption	Biochemical	Chattopadhyay et al., 1998
K cells	${\text{Ca}}_{\text{o}}^{2+}$, amino acid	↑GIP↑insulin/nutrient utilization	Pharmacological	Mace et al., 2012
L cells	${\text{Ca}}_{\text{o}}^{2+}$, amino acid, peptide	↑GLP-1↑insulin/nutrient utilization	Pharmacological	Leech and Habener, 2003; Mace et al., 2012; Diakogiannaki et al., 2013; Pais et al., 2016
Colon
Surface & crypt cells (ap & bl)	${\text{Ca}}_{\text{o}}^{2+}$, polyamine, R568	↑absorption; ↓secretion	Pharmacogenetic	Chattopadhyay et al., 1998; Cheng et al., 2002; Cheng, 2012
		↑barrier function; ↑gut immunity	Pharmacogenetic	Jouret et al., 2013; Macleod, 2013b; Cheng et al., 2014
		↓proliferation; ↑differentiation	Pharmacogenetic	Chakrabarty et al., 2003; Rey O et al., 2012; Aggarwal et al., 2015
		↓colon cancer	Pharmacogenetic	Kallay et al., 2000; Sheinin et al., 2000; Singh and Chakrabarty, 2013; Aggarwal et al., 2015; Singh et al., 2015
CELLS THAT REGULATE OTHER FUNCTIONS
Myofibroblasts	${\text{Ca}}_{\text{o}}^{2+}$	↑wnt5a and BMP-2 secretion	Biochemical	Peiris et al., 2007; Pacheco and Macleod, 2008
ENS	peptide, R568	↓secretion; ↓motility	Pharmacological	Chattopadhyay et al., 1998; Cheng, 2012; Muramatsu et al., 2014
Immune cells	${\text{Ca}}_{\text{o}}^{2+}$	↓inflammation	Biochemical	Kelly et al., 2011

Ala, alanine; ap, apical membrane; bl, basolateral membrane; ${\text{Ca}}_{\text{o}}^{2+}$, extracellular calcium; CCK, cholecystokinin; ENS, enteric nervous system; GIP, glucose-dependent insulinotropic peptide; GLP-1, glucagon-like peptide-1; Phe, phenylalanine; PYY, peptide tyrosine tyrosine; Trp, tryptophan.