Review
Copyright ©The Author(s) 2018.
World J Gastroenterol. Sep 28, 2018; 24(36): 4119-4131
Published online Sep 28, 2018. doi: 10.3748/wjg.v24.i36.4119
Table 1 Examples of orthosteric agonists and allosteric modulators of the calcium-sensing receptor[13-15]
Ligand typeClass and examplesReported effects on inflammationReported effects on cancerRef.
Orthosteric agonistsInorganic divalent and trivalent cations: Zn2+ 1Ca2+; Mg2+; Gd3+Reduces inflammation in mouse models of colitisHigh Ca2+ intake: Associated low risk for CRC[16-18]
Intake is correlated with reduced inflammation
Polyamines: Spermine spermidine, putrescineIncrease airway inflammation and hyperresponsivenessReduce pancreatic cancer growth in mice[5,19]
Aminoglycoside antibiotics: Neomycin, gentamycin, tobramycin--
Basic polypeptides: poly-l-arginine, 1poly-l-lysine, and amyloid β-peptidesInduces airway inflammation-[5,20]
Reduces inflammation in mouse models of colitis
Combined orthosteric and allosteric modulatorsD-amino-acid polypeptides: Etelcalcetide--
L-amino acids: Phenylalanine, tryptophan--
Glutamyl dipeptides: 1γ-Glu-Val, 1γ-Glu-CysReduces inflammation in mouse models of colitis-[21]
Allosteric modulators (calcimimetics and calcilytics)Small molecule calcimimetics: Sensipar (1Cinacalcet HCl), NPS-R568, GSK3004774Increases airway hyperresponsivenessTreatment of parathyroid tumours[5,22-24]
Inhibits neuroblastoma tumour growth
Reduces hypercalcaemia of malignancy
Small molecule calcilytics: 1NPS-2143, Calhex, Ronacalaret, AXT-914Reduces pulmonary inflammation and airway hyperresponsiveness in rodents-[5,25,26]