title: Regulation of cytosolic calcium by parathyroid hormone and oscillations of cytosolic calcium in fibroblasts from normal and pseudohypoparathyroid patients.
abstract: The second messengers for PTH action on fibroblasts have not been determined. The hypothesis that Ca2+ is a second messenger was examined by spectrofluorometric measurement of cytosolic calcium ([Ca2+]i), of fura-2-loaded human dermal skin fibroblasts. PTH induced: 1) transient elevations of [Ca2+]i due to both Ca2+ influx and intracellular release which were independent of CAMP generation, and 2) membrane depolarization. PTH treatment of fibroblasts depolarized by KCl induced oscillations of [Ca2+]i, but spontaneous oscillatory activity was not observed. Transient elevations of [Ca2+]i similar to that induced by PTH were observed with PTH-related peptide (PTHrp). PTH regulation of [Ca2+]i was normal in fibroblasts from patients with pseudohypoparathyroidism (PHP) type Ia (deficiency of the stimulatory GTP-binding protein, Gs), but PTH induced transient decreases in [Ca2+]i in fibroblasts from patients with PHP type Ib (defective PTH receptor). Both PHP Ia and Ib fibroblasts exhibited: 1) spontaneous [Ca2+]i oscillations, possibly due to voltage gated Ca2+ entry and Ca2+ induced Ca2+ release; and 2) greater sensitivity than normal fibroblasts for release of Ca2+ from intracellular stores when [Ca2+]i was decreased by lowering external Ca2+.
  
  
  CONCLUSIONS
  1) PTH-induced transient elevations in [Ca2+]i in normal fibroblasts result from Ca2+ entry and intracellular release which are independent of CAMP generation; 2) [Ca2+]i homeostasis is altered in PHP fibroblasts, resulting in Ca2+ oscillations; 3) PTH regulation of [Ca2+]i is altered in PHP Ib, but not in PHP Ia fibroblasts.
authors.affiliation: Renal Divisions, Jewish Hospital of St. Louis, Washington University School of Medicine, Missouri 63110.
authors.forename: A
authors.initials: A
authors.lastname: Gupta
authors.forename: K J
authors.initials: KJ
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Miyauchi
authors.forename: K A
authors.initials: KA
authors.lastname: Hruska
mesh_terms: D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D010281:Parathyroid Hormone / Q000502:physiology*; D011547:Pseudohypoparathyroidism / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism; D018016:Receptors, Parathyroid Hormone; D012016:Reference Values
chemical_list: D010281:Parathyroid Hormone; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D002118:Calcium