title: Endothelin-induced calcium signaling and secretion in chief cells and fibroblasts from pathological human parathyroid glands.
abstract: 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.
authors.affiliation: Department of Surgery, University Hospital, Uppsala, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Ridefelt
authors.forename: P
authors.initials: P
authors.lastname: Hellman
authors.forename: T
authors.initials: T
authors.lastname: Carling
authors.forename: J
authors.initials: J
authors.lastname: Rastad
authors.forename: G
authors.initials: G
authors.lastname: Akerström
mesh_terms: 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
chemical_list: D019332:Endothelin-1; D019334:Endothelin-3; D010281:Parathyroid Hormone; D002118:Calcium