Effects of prostaglandins and other drugs on the cyclic AMP content of cultured bone cells

Abstract

Prostaglandins of the E-series (PGE 1 and PGE 2) may be involved in disease-related, localized loss of bone. E-prostaglandins increase the cyclic AMP content of many cells; and, to determine if their effects on bone are mediated by cyclic AMP, we examined the effects of E-prostaglandins and of other agents on the cyclic AMP content of cultured bone cells. PGE 2 produced a rapid, marked and dose-related increase in the cyclic AMP content of confluent monolayers of bone cells isolated from newborn rat calvaria. At 2.8 × 10 −6 M, PGE 1 and PGE 2 had approximately the same effect, while the effect of PGF 2α was much less pronounced. In the presence of theophylline, PGE 2 had a more marked effect than parathyroid hormone (PTH) and the combination of PGE 2 and PTH had a synergistic effect. The divalent, cationic, ionophore, A23187, produced an increase in cellular cyclic AMP and had an additive effect in combination with PGE 2. Synthetic salmon calcitonin (CT), which inhibits the bone resorptive effect of PGE 2, increased cellular cyclic AMP and had an additive effect in combination with PGE 2. A prostaglandin antagonist, SC-19220, partially inhibited the resorptive effect of PGE 2 and reduced its effect on cellular cyclic AMP. The calcium antagonist, D600, inhibited the bone resorptive effects of PGE 2 but had no effect on increased cellular cyclic AMP produced by PGE 2. The marked effect of PGE 2 on bone cell cyclic AMP suggests that this action is involved in the mechanism of PGE 2-related bone loss. The fact that agents with different effects on PGE 2-induced increases in cellular cyclic AMP can inhibit its resorptive actions, suggests that PGE 2-induced changes in cyclic AMP may be related less to its resorptive actions than to its inhibitory effect on bone formation.