Oral expressions and functional analyses of the extracellular calcium-sensing receptor (CaSR) in chicken

Abstract

In vertebrates, the extracellular calcium-sensing receptor (CaSR) plays a key role in calcium homeostasis by sensing slight changes in extracellular Ca2+. CaSR is also expressed in mammals including rodent taste cells and is involved in sensing kokumi, a rich, savory quality that enhances the intensities of salty, sweet, and umami tastes. In this study, we focused on chicken CaSR (cCaSR) since calcium is an essential nutrient that is necessary for making eggshell and for the extremely rapid initial growth of bones. First we confirmed that cCaSR is expressed in taste cells. Next we cloned the cCaSR gene from kidney and transiently transfected human embryonic kidney 293 T (HEK293T) cells with the recombinant cCaSR, or empty vector and looked for the agonists and allosteric modulators (including kokumi substances) of cCaSR by Ca2+ imaging. We found that cCaSR was activated by extracellular Ca2+ and Mg2+ in a dose dependent manner. Several L-amino acids and kokumi substances such as glutathione enhanced the response of cCaSR. In addition, NPS2143 as a negative allosteric modulator of human CaSR negatively modulated the response of cCaSR. These results suggest that cCaSR can sense extracellular Ca2+ and Mg2+ as well as positive and negative allosteric modulators. Taken together, the results imply that CaSR might be a multifunctional receptor for calcium, amino acids, and kokumi substances in chicken. The present finding that functional CaSR is expressed in the chicken oral tissues will allow us to further elucidate the physiological role of CaSR in the chickens' taste sense, and to create new feeds that will contribute to the poultry industry.

Exploring novel Kokumi peptides in Agaricus bisporus: selection, identification, and tasting mechanism investigation through sensory evaluation and computer simulation analysis

“…S2. † Hikaru Omori et al 47 validated the enhanced response of CaSR using L-amino acids and Kokumi substances like glutathione, confirming the expression of CaSR in taste cells and elucidating the physiological role of CaSR in taste. This provided a method and theoretical basis for exploring Kokumi.…”

Silicon-rhodamine functionalized evocalcet probes (EvoSiR) potently and selectively label calcium sensing receptors (CaSR) in vitro, in vivo and ex vivo

“…The calcium sensing receptor (CaSR) is the major class C G-protein coupled receptor (GPCR) that integrates extracellular calcium signals, and controls calcium homeostasis in the parathyroid glands 3 and kidneys 4 by regulating parathyroid hormone production. However, the apparently ubiquitous expression of the CaSR across tissues 5 underscores the less understood roles of CaSR signaling in a wide variety of physiological processes, for instance its involvement in airway smooth muscle contractility 6 , inflammation 7 , taste modulation 8 and neuronal excitability 9,10 . Furthermore, dysfunctional CaSR signaling has been implicated in non-calcitropic diseases such as asthma 11 , colorectal inflammatory conditions such as inflammatory bowel disease (IBD) 12 as well as Alzheimer's 13 and cardiovascular disease (CVD) 14 , making this GPCR an attractive potential target for the development of novel therapeutic interventions and as possible disease marker.…”

The avian taste system

“…In addition to T1R1-T1R3, other amino acid or peptide receptors such as mGluR1, mGluR4, GPR92, CaSR, GPR139, and GPRC6A have also been reported to be functional in the avian oral cavity (Baldwin et al, 2014;Cheled-Shoval et al, 2014;. For example, CaSR is expressed in chicken taste buds and its activity increased responding to alanine, tryptophane, and phenylalanine (Omori et al, 2022). However, low extracellular calcium negatively affected the activation of CaSR by these amino acids (Omori et al, 2022).…”

“…For example, CaSR is expressed in chicken taste buds and its activity increased responding to alanine, tryptophane, and phenylalanine (Omori et al, 2022). However, low extracellular calcium negatively affected the activation of CaSR by these amino acids (Omori et al, 2022). Furthermore, CaSR may play an essential role in sensing calcium which is discussed in Section 4.4.…”