Taste Cells of the Type III Employ CASR to Maintain Steady Serotonin Exocytosis at Variable Ca2+ in the Extracellular Medium

Abstract

Type III taste cells are the only taste bud cells which express voltage-gated (VG) Ca2+ channels and employ Ca2+-dependent exocytosis to release neurotransmitters, particularly serotonin. The taste bud is a tightly packed cell population, wherein extracellular Ca2+ is expected to fluctuate markedly due to the electrical activity of taste cells. It is currently unclear whether the Ca2+ entry-driven synapse in type III cells could be reliable enough at unsteady extracellular Ca2. Here we assayed depolarization-induced Ca2+ signals and associated serotonin release in isolated type III cells at varied extracellular Ca2+. It turned out that the same depolarizing stimulus elicited invariant Ca2+ signals in type III cells irrespective of bath Ca2+ varied within 0.5–5 mM. The serotonin release from type III cells was assayed with the biosensor approach by using HEK-293 cells co-expressing the recombinant 5-HT4 receptor and genetically encoded cAMP sensor Pink Flamindo. Consistently with the weak Ca2+ dependence of intracellular Ca2+ transients produced by VG Ca2+ entry, depolarization-triggered serotonin secretion varied negligibly with bath Ca2+. The evidence implicated the extracellular Ca2+-sensing receptor in mediating the negative feedback mechanism that regulates VG Ca2+ entry and levels off serotonin release in type III cells at deviating Ca2+ in the extracellular medium.

PI3 kinase inhibitor PI828 uncouples aminergic GPCRs and Ca2+mobilization irrespectively of its primary target

“…Cells of rat glioma (C6) responded to histamine with Ca 2+ transients as well. Serotonin-induced Ca 2+ signaling were studied in CHO/5-HT 2C cells that stably expressed the recombinant serotonin 5-HT 2C receptor (Cherkashin et al, 2022). Given that cells of the above-mentioned lines were not responsive, in terms of Ca 2+ signaling, to dopamine, dopaminergic signaling was not studied here.…”

“…The CHO/5-HT 2C line, which was derived from CHO-K1 cells, was a monoclonal cell line that stably expressed serotonin 5-HT 2C receptors cloned from the mouse brain (Cherkashin et al, 2022).…”

Effect of kokumi taste-active γ-glutamyl peptides on amiloride-sensitive epithelial Na+ channels in rat fungiform taste cells

“…CaSR senses kokumi substances in taste tissues and seems to be expressed by Type II and Type III cells [ 9 , 10 , [21] , [22] , [23] , [24] ]. In a subset of Type III cells, CaSR is functional and is involved in the regulation of serotonin release [ 25 ]. It is not known whether CaSR is expressed in sodium-taste cells.…”

“…Furthermore, they found that blocking calcium-sensing receptor (CaSR) had no effect on ENaC activation by arginyl dipeptides. These findings are significant because CaSR is thought to function as a kokumi taste receptor [ 9 , 21 , 22 ] in taste tissues [ 10 , [23] , [24] , [25] ].…”

Agonist-Induced Ca2+ Signaling in HEK-293-Derived Cells Expressing a Single IP3 Receptor Isoform

“…Previously, we studied Ca 2+ signaling induced by GPCR agonists, including ATP, UTP, adenosine, ACh, 5-HT, and glutamate, in cells of diverse types [29][30][31][32]. The assayed cells universally responded to Ca 2+ -mobilizing agonists in an "all-or-nothing" manner: They either were irresponsive to a particular agonist at subthreshold concentrations or generated quite similar Ca 2+ signals at different agonist doses above the threshold (see Figure 1 below).…”