Extracellular ATP and UTP Increase Cytosolic Free Calcium by Activating a Common P 2U-Receptor in Single Human Thyrocytes

In single human thyrocytes extracellular ATP, ATP- γ-S, ADP and UTP caused a concentration dependent biphasic increase in [Ca 2+] i Consistent with a P 2u-receptor the rank-order of potency was ATP = UTP > ATP- γ-S > ADP, and cross-desensitization of the Ca 2+ responses occurred between ATP and UTP. The initial transient peak in [Ca 2+] i was resistent to extracellular Ca 2+ depletion which demonstrates mobilisation of internal Ca 2+ by IP 3 whose formation was rapidly enhanced by ATP and UTP. By contrast, the sustained plateau phase required influx of external Ca 2+. Ca 2+ influx occurs most likely through a capacitative Ca 2+ entry mechanism, which was shown to exist in these cells by experiments performed with thapsigargin. Thus, low micromolar concentrations of extracellular ATP and UTP activate a common P 2u-receptor coupled to the Ca 2+-phosphatidylinositol signalling cascade in human thyrocytes. This indicates that extracellular nucleotides from various sources might play an important role in human thyroid physiology.