Thrombin and parathyroid hormone mobilize intracellular calcium in rat osteosarcoma cells by distinct pathways

Michael Babich, Hester Choi, Randolph M. Johnson, Kathleen L. King, Gay E. Alford, Robert A. Nissenson

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


The mechanisms by which PTH and thrombin mobilize intracellular Ca2+ (Cai 2+) were examined in UMR 106-H5 rat osteosarcoma cells. Bovine PTH-(1-34) (24 pM to 240 nM) produced a dose-dependent increase in Cai 2+ (EC50, 3 nM), which returned to baseline within 75 sec. Human α-thrombin produced an increase in Cai 2+ (ECmax, 10 U/ml) which was similar to that of PTH with respect to both magnitude and time course. Chelation of extracellular calcium with 5.0 mM EGTA did not alter the Cai 2+ response to either PTH or thrombin. When added together at maximally effective concentrations, PTH and thrombin produced additive effects on Cai 2+ in the presence and absence of EGTA. The additive effects of PTH and thrombin on Cai 2+. were confirmed at the single cell level, using laser-based image analysis. Bradykinin (1 μM) produced a significant increase in Cai 2+ in UMR 106-H5 cells which was of lesser magnitude than the peak 2- to 3-fold increase elicited by PTH or thrombin. Preexposure of cells to 10 U/ml thrombin for 2 min abolished the Cai 2+ response to bredykinin, whereas preexposure to 240 nM PTH had no effect on the Cai 2+ response to bradykinin. Thrombin elicited a rapid increase in the accumulation of 3H-labeled inositol phosphates (IP2 and IP3) in UMR 106-H5 cells, with increases in [3H]1,4,5-IP3 detectable as early as 15 sec after the addition of thrombin. Bradykinin increased [3H]IP production to a lesser extent than thrombin, whereas PTH neither increased [3H]IP accumulation nor potentiated the [3H]IP response to thrombin. The results suggest that thrombin and bradykinin mobilize Cai 2+ from a shared IP3-responsive calcium pool, whereas PTH may use signals in addition to 1,4,5-IP3 to mobilize calcium from a distinct cellular calcium pool. Alternatively, specific calcium compartmentalization exists, and there is differential coupling of these agonists to the 1,4,5-IPa/Cai 2+. pathway.

Original languageEnglish (US)
Pages (from-to)1463-1470
Number of pages8
Issue number3
StatePublished - Sep 1991

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism


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