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-gamma-S, ADP and UTP caused a concentration dependent biphasic increase in [Ca2+](i) Consi stent with a P-2u-receptor the rank-order of potency was ATP = UTP > A TP-gamma-S > ADP, and cross-desensitization of the Ca2+ responses occu rred between ATP and UTP. The initial transient peak in [Ca2+](i) was resistent to extracellular Ca2+ depletion which demonstrates mobilisat ion of internal Ca2+ by IP3 whose formation was rapidly enhanced by AT P and UTP. By contrast, the sustained plateau phase required influx of external Ca2+. Ca2+ influx occurs most likely through a capacitative Ca2+ entry mechanism, which was shown to exist in these cells by exper iments performed with thapsigargin. Thus, low micromolar concentration s of extracellular ATP and UTP activate a common P-2u-receptor coupled to the Ca2+-phosphatidylinositol signalling cascade in human thyrocyt es. This indicates that extracellular nucleotides from various sources might play an important role in human thyroid physiology. (C) 1995 Ac ademic Press, Inc.