Endothelin-induced calcium signaling and secretion in chief cells and fibroblasts from pathological human parathyroid glands.
Endothelins (ETs) are 21 amino acid peptides with vasoactive and mitogenic properties. The three isopeptides (ET-1, -2, and -3) and their receptors (E1A and ETB subtypes) display expression in numerous tissues and possibly mediate autocrine/paracrine actions. The present investigation shows that ET-1 triggers biphasic increases of the concentration of cytoplasmic Ca2+ ([Ca2+]i) in pathological human parathyroid cells. Both the peak and sustained [Ca2+]i increase, as well as the proportion of responding cells, are dose-dependent in the 10(-10)-10(-7) mol/L range of ET-1. In absence of external Ca2+, the ET-1-induced [Ca2+]i peak is attenuated. ET-3 has no effect on [Ca2+]i indicating functional dominance of the ETA receptor subtype. ET-1 (10 nmol/L) lowers parathyroid hormone secretion in 0.5 mmol/L but not in higher external Ca2+ concentrations, and parathyroid cell ET release is inhibited by increases of external Ca2+. Fibroblasts overgrowing the parathyroid chief cells during monolayer culture respond to ET-1 with biphasic [Ca2+]i increases or repetitive [Ca2+]i spikes, but show no response to elevation of external Ca2+. These findings imply that ET secretion and ET receptor expression may constitute an autocrine/paracrine mechanism in the regulation of human PTH secretion.
Ridefelt
P
P
Department of Surgery, University Hospital, Uppsala, Sweden.
Hellman
P
P
Carling
T
T
Rastad
J
J
Akerström
G
G
D000236:Adenoma / Q000473:pathology / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D019334:Endothelin-3 / Q000378:metabolism / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D006801:Humans; D006961:Hyperparathyroidism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D006965:Hyperplasia; D018761:Multiple Endocrine Neoplasia Type 1 / Q000473:pathology / Q000503:physiopathology; D010280:Parathyroid Glands / Q000473:pathology / Q000503:physiopathology*; D010281:Parathyroid Hormone / Q000378:metabolism; D010282:Parathyroid Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured
D019332:Endothelin-1; D019334:Endothelin-3; D010281:Parathyroid Hormone; D002118:Calcium