L-amino acids promote calcitonin release via a calcium-sensing receptor: Gq/11-mediated pathway in human C-cells: supplemental figures

Human calcitonin release is promoted by elevated extracellular Ca2+ (Ca2+o) concentration acting, at least in part,via the calcium-sensing receptor (CaSR). The CaSR is positively modulated by L-amino acids including the aromaticamino acids L-Phe and L-Trp. To investigate the effect of L-amino acids on human calcitonin secretion we selectedthyroid TT cells and exposed them to various Ca2+o concentrations in the absence or presence of L-Phe, plasma-likemixtures of L-amino acids, or the clinically effective positive modulator (calcimimetic), cinacalcet. In the presence ofL-Phe or plasma-like mixtures of amino acids, TT cells exhibited enhanced Ca2+o sensitivity in assays of calcitoninrelease and intracellular Ca2+ (Ca2+i) mobilization. Furthermore, the effect of elevated Ca2+o and L-Phe oncalcitonin release was markedly suppressed by the calcilytic NPS-2143. These effects were dependent uponCaSR-mediated activation of Gq/11 as revealed by the specific inhibitor YM-254890. The findings support thehypothesis that calcitonin release is stimulated by increases in plasma L-amino acid levels as well as elevatedextracellular Ca2+. They also demonstrate that stimulated calcitonin release as well as basal levels of calcitoninsecretion are mediated by a CaSR:Gq/11 signaling mechanism.
This dataset comprises of 4 files; two supplemental figures, methods for supplemental figures document, and supplemental figure legends.