Metabolic, but not respiratory, acidosis increases bone PGE2 levels and calcium release

Abstract

First published July 12, 2001; 10.1152/ajprenal.00355.2001.— A decrease in blood pH may be due to either a reduction in bicarbonate concentration ([HCO[Formula: see text]]; metabolic acidosis) or to an increase in Pco 2 (respiratory acidosis). In mammals, metabolic, but not respiratory, acidosis increases urine calcium excretion without altering intestinal calcium absorption, indicating that the additional urinary calcium is derived from bone. In cultured bone, chronic metabolic, but not respiratory, acidosis increases net calcium efflux ( J Ca), decreases osteoblastic collagen synthesis, and increases osteoclastic bone resorption. Metabolic acidosis increases bone PGE2production, which is correlated with J Ca, and inhibition of PGE2 production inhibits this acid-induced J Ca. Given the marked differences in the osseous response to metabolic and respiratory acidosis, we hypothesized that incubation of neonatal mouse calvariae in medium simulating respiratory acidosis would not increase medium PGE2 levels, as observed during metabolic acidosis. To test this hypothesis, we determined medium PGE2 levels and J Ca from calvariae incubated at pH ∼7.1 to model either metabolic (Met; [HCO[Formula: see text]] ∼11 mM) or respiratory (Resp; Pco 2 ∼83 Torr) acidosis, or at pH ∼7.5 as a control (Ntl). We found that after 24–48 and 48–51 h in culture, periods when cell-mediated J Capredominates, medium PGE2 levels and J Ca were increased with Met, but not Resp, compared with Ntl, and there was a direct correlation between medium PGE2 levels and J Ca. Thus metabolic, but not respiratory, acidosis induces the release of bone PGE2, which mediates J Ca from bone.