title: Metabolic, but not respiratory, acidosis increases bone PGE(2) levels and calcium release.
abstract: A decrease in blood pH may be due to either a reduction in bicarbonate concentration ([HCO(3)(-)]; 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 PGE(2) production, which is correlated with J(Ca), and inhibition of PGE(2) 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 PGE(2) levels, as observed during metabolic acidosis. To test this hypothesis, we determined medium PGE(2) levels and J(Ca) from calvariae incubated at pH approximately 7.1 to model either metabolic (Met; [HCO(3)(-)] approximately 11 mM) or respiratory (Resp; PCO(2) approximately 83 Torr) acidosis, or at pH approximately 7.5 as a control (Ntl). We found that after 24-48 and 48-51 h in culture, periods when cell-mediated J(Ca) predominates, medium PGE(2) levels and J(Ca) were increased with Met, but not Resp, compared with Ntl, and there was a direct correlation between medium PGE(2) levels and J(Ca). Thus metabolic, but not respiratory, acidosis induces the release of bone PGE(2), which mediates J(Ca) from bone.
authors.affiliation: Nephrology Unit, Department of Medicine, University of Rochester School of Medicine, Rochester, New York 14642, USA. David_Bushinsky@URMC.Rochester.edu
authors.forename: D A
authors.initials: DA
authors.lastname: Bushinsky
authors.forename: W R
authors.initials: WR
authors.lastname: Parker
authors.forename: K M
authors.initials: KM
authors.lastname: Alexander
authors.forename: N S
authors.initials: NS
authors.lastname: Krieger
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000142:Acidosis, Respiratory / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001639:Bicarbonates / Q000032:analysis; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002245:Carbon Dioxide / Q000737:chemistry; D003470:Culture Media / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D007700:Kinetics; D051379:Mice; D009924:Organ Culture Techniques; D010313:Partial Pressure
chemical_list: D001639:Bicarbonates; D003470:Culture Media; D002245:Carbon Dioxide; D015232:Dinoprostone; D002118:Calcium