The Effect of Acute Acidosis on the Uptake of Parathyroid Hormone and the Production of Adenosine 3′,5′-Monophosphate by Isolated Perfused Bone*

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Abstract
Increased bone resorption and negative calcium balance are known to occur in metabolic acidosis. However, the mechanisms underlying these effects are unclear. The present studies examine the effects of lowering pH in vitro on the uptake and action of parathyroid hormone (PTH) in an isolated perfused canine tibia preparation. Both the arterio-venous difference for immunoreactive PTH (iPTH) across bone and cAMP production by isolated bone during infusion of synthetic bovine PTH·(1–34) [bPTH·(1–34)] were studied. At perfusate pH 7.4 (Krebs-Henseleit buffer with 1% bovine serum albumin gassed with 95% O2-5% CO2), basal cAMP production was 6.3 ± 1.8 pmol/min. After the addition of synthetic bPTH·(1–34) (3 ng/ml) to the perfusate, cAMP production rose to 25.9 ± 4.8 pmol/min, and the arterio-venous difference for iPTH across the perfused bone was 35 ± 2% in eight studies. In 10 additional studies after initial control periods for cAMP production (7.6 ± 1.6 pmol/min), the perfusate pH was lowered to 7.0–7.1 by adding HCl. The lower pH resulted in an increased cAMP production by bone, reaching a peak value of 38.5 ± 8 pmol/min; after the addition of synthetic bPTH·(1–34) (3 ng/ml), cAMP production rose to a peak of 56 ± 8.6 pmol/min (6 studies). The greater cAMP production with lower pH perfusates was associated with an increase in the arterio-venous difference for iPTH across bone to 55 ± 1%, a value significantly different from the 35 ± 2% extraction observed when the perfusate pH was 7.4. Acidosis induced by increasing perfusate pCO2 (simulated respiratory acidosis) did not affect PTH uptake or cAMP production by bone. These studies indicate that the uptake of iPTH by bone and the production of cAMP are markedly increased by simulated metabolic acidosis. It is suggested that acute metabolic acidosis may increase bone resorption by increasing the uptake of PTH and the production of cAMP by the skeleton. (Endocrinology106: 1607, 1980)