Prostaglandins enhance parathyroid hormone-evoked increase in free cytosolic calcium concentration in osteoblast-like cells

Abstract

Prostaglandins (PGs) are autocrine or paracrine hormones that may interact with circulating hormones such as parathyroid hormone (PTH) in bone. We examined the interaction of the PGs, PGF 2α, PGE 2, and 6-keto-PGF 1α with PTH to enhance the rapid, initial transient rise in free cytosolic calcium ([Ca 2+] i) and cAMP levels stimulated by PTH. Pretreatment of UMR-106, MC3T3-E1, and neonatal rat calvarial osteoblast-like cells by PGs resulted in an enhancement of the early transient rise in [Ca 2+] i stimulated by PTH. PGF 2α was approximately 100 times more potent than PGE 2. PGE 2 itself was more potent than 6-keto-PGF 1α in enhancing PTH-stimulated rise in [Ca 2+] i. Near-maximal augmentation was achieved at PGF 2α doses of 10 nM and PGE 2 of 1 μM. The degree of augmentation in [Ca 2+] i by PGF 2α was independent of preincubation time. PGF 2α pretreatment did not alter the EC 50 for the PTH-induced [Ca 2+] i increase but only the extent of rise in [Ca 2+] i at each dose of PTH. The augmented increase in [Ca 2+] i was mostly due to enhanced PTH-mediated release of Ca 2+ from intracellular stores. PGF 2α did not stimulate an increase in PTH receptor number as assessed by [ 125I]-PTH-related peptide binding. PG pretreatment partially reversed PTH inhibition of cell proliferation, suggesting that an increase in [Ca 2+] i may play a role in tempering the anti-proliferative effect of PTH mediated by cAMP. These studies suggest a new mode by which PGs can affect cellular activity.