Abstract
Recently, we reported that calcium-sensing receptor (CaSR) is a receptor for kokumi substances, which enhance the intensities of salty, sweet and umami tastes. Furthermore, we found that several γ-glutamyl peptides, which are CaSR agonists, are kokumi substances. In this study, we elucidated the receptor cells for kokumi substances, and their physiological properties. For this purpose, we used Calcium Green-1 loaded mouse taste cells in lingual tissue slices and confocal microscopy. Kokumi substances, applied focally around taste pores, induced an increase in the intracellular Ca2+ concentration ([Ca2+]i) in a subset of taste cells. These responses were inhibited by pretreatment with the CaSR inhibitor, NPS2143. However, the kokumi substance-induced responses did not require extracellular Ca2+. CaSR-expressing taste cells are a different subset of cells from the T1R3-expressing umami or sweet taste receptor cells. These observations indicate that CaSR-expressing taste cells are the primary detectors of kokumi substances, and that they are an independent population from the influenced basic taste receptor cells, at least in the case of sweet and umami.
Highlights
The extracellular calcium-sensing receptor, CaSR, is a classic seven-transmembrane-spanning, G protein-coupled receptor (GPCR) belonging to Family C of the superfamily of GPCRs [1]
We identified a population (6.5%) of taste cells in the circumvallate papillae that responds to kokumi substances
This value is comparable with the immunohistochemistry results (6.8% CaSRpositive cells/taste bud)
Summary
The extracellular calcium-sensing receptor, CaSR, is a classic seven-transmembrane-spanning, G protein-coupled receptor (GPCR) belonging to Family C of the superfamily of GPCRs [1]. CaSR has been identified in several cells and tissues, including the parathyroid gland and kidney. It plays a central role in extracellular calcium homeostasis in mammals [2]. An increase in the blood calcium level is sensed by CaSR, which in turn suppresses parathyroid hormone secretion, stimulates calcitonin secretion, and induces urinary calcium excretion to reduce blood calcium to normal levels. It has become apparent that CaSR is expressed in the parathyroid glands and kidney, and in many other tissues such as liver, heart, lung, gastrointestinal tract, pancreas and the central nervous system, suggesting that it is involved in a range of biological functions [3]. It has been reported that CaSR is activated by several types of substances including cations such as Ca2+, Mg2+ and Gd3+, basic peptides such as protamine and polylysine, and polyamines such as spermine [3]
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