Adenosine triphosphate, bradykinin, and thyrotropin-releasing hormone regulate the intracellular Ca2+ concentration and the 45Ca2+ efflux of human thyrocytes in primary culture.
The hormonal stimulation of phospholipase C and the consequent activation of the Ca2+-phosphatidylinositol cascade in eukaryotic cells is associated with modifications of the [Ca2+]i (intracellular Ca2+ concentration) which modulates cellular functions. In this study, these modifications were investigated in primary cultures of human thyroid cells. The mean apparent basal [Ca2+]i of human thyrocytes measured using the intracellularly trapped fluorescent indicator Quin-2 was found to be 89 +/- 16 nM (n = 49). ATP and, to a lesser extent, ADP, but not AMP or adenosine, elicited a concentration-dependent biphasic rise in human thyrocytes [Ca2+]i and increased their 45Ca2+ efflux. The first transient phase of the [Ca2+]i rise induced by ATP was resistant to extracellular Ca2+ depletion, whereas the second sustained phase was abolished in these conditions. This suggests that although the first phase of this response involves a release of Ca2+ from intracellular stores, the second phase requires extracellular Ca2+ influx. The response of human thyrocytes to analogs of ATP is compatible with a P2-purinergic effect of ATP on these cells. Bradykinin and TRH affected the human thyrocyte [Ca2+]i and 45Ca2+ efflux similarly to ATP. The human thyrocyte [Ca2+]i and the 45Ca2+ efflux were not modified by carbachol, a nonhydrolyzable analog of acetylcholine. The present results suggest the presence of P2-purinergic receptors to ATP and of receptors to TRH and bradykinin on human follicular thyroid cells. They also confirm that the Ca2+-phosphatidylinositol cascade is present in these cells and suggest that this cascade is modulated by ATP, TRH, and bradykinin. As this cascade is involved in the regulation of protein iodination, and therefore of thyroid hormones synthesis, these agents might have an important role in the regulation of the thyroid function.
Raspé
E
E
I.R.I.B.H.N., Free University of Brussels, School of Medicine, Belgium.
Andry
G
G
Dumont
J E
JE
D000227:Adenine Nucleotides / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010716:Phosphatidylinositols / Q000502:physiology; D013961:Thyroid Gland / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D000227:Adenine Nucleotides; D010716:Phosphatidylinositols; D013973:Thyrotropin-Releasing Hormone; D000255:Adenosine Triphosphate; D002217:Carbachol; D000241:Adenosine; D001920:Bradykinin; D002118:Calcium