Parathyroid hormone acutely elevates intracellular calcium in osteoblastlike cells

Changes in cytoplasmic calcium concentration ([Ca²⁺](i)) activate numerous cellular processes thus mediating the effects of a number of hormones, but whether this mechanism is involved in the activation of osteoblasts by parathyroid hormone (PTH) remains uncertain. To examine this question, [Ca²⁺](i) has been measured in suspensions of UMR 106 cells, a rodent osteosarcoma cell line with an osteoblastic phenotype. Basal [Ca²⁺](i) was 137 ± 3.7 nM (n = 60) and after the addition of rat PTH-(1-34) [rPTH-(1-34)] there was a rapid, dose-related increase with return to base line within 1 min. Half-maximal stimulation was produced by 5 x 10^-8 M rPTH-(1-34). Complexing of intracellular calcium by EGTA addition immediately before that of rPTH did not affect the calcium transient; neither did MnCl₂ (10^-4 M) nor diltiazem (10^-4 M). Verapamil (10^-5 M) reduced the [Ca²⁺](i) peak height after rPTH to 0.48 ± 0.14 of control (n = 7). 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoic acid and dantrolene both reduced the [Ca²⁺](i) response to rPTH (0.65 ± 0.08 and 0.29 ± 0.13 of control, respectively). Forskolin (10^-6 and 10^-5 M) produced a slight [Ca²⁺](i) transient smaller in amplitude than seen with PTH. It is concluded that PTH mobilizes an intracellular calcium pool in these osteoblastlike cells, and the predominant mechanism for this is independent of cAMP.