Extracellular ATP and UTP increase cytosolic free calcium by activating a common P2u-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. Consistent with a P2u-receptor the rank-order of potency was ATP = UTP > ATP-gamma-S > ADP, and cross-desensitization of the Ca2+ responses occurred between ATP and UTP. The initial transient peak in [Ca2+]i was resistant to extracellular Ca2+ depletion which demonstrates mobilisation of internal Ca2+ by IP3 whose formation was rapidly enhanced by ATP 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 experiments performed with thapsigargin. Thus, low micromolar concentrations of extracellular ATP and UTP activate a common P2u-receptor coupled to the C(a2+)-phosphatidylinositol signalling cascade in human thyrocytes. This indicates that extracellular nucleotides from various sources might play an important role in human thyroid physiology.
Schöfl
C
C
Department of Clinical Endocrinology, Medizinische Hochschule Hannover, Germany.
Rössig
L
L
Pötter
E
E
von zur Mühlen
A
A
Brabant
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D016257:Fura-2; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D014544:Uridine Triphosphate / Q000378:metabolism*
D011983:Receptors, Purinergic; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D002118:Calcium; D016257:Fura-2; D014544:Uridine Triphosphate