Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog

Abstract

of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog. Am J Physiol Endocrinol Metab 286: E780 -E785, 2004. First published January 13, 2004 10.1152/ajpendo.00473.2003.-Recently, we showed that both acute metabolic acidosis and respiratory acidosis stimulate parathyroid hormone (PTH) secretion in the dog. To evaluate the specific effect of acidosis, ionized calcium (iCa) was clamped at a normal value. Because iCa values normally increase during acute acidosis, we now have studied the PTH response to acute metabolic and respiratory acidosis in dogs in which the iCa concentration was allowed to increase (nonclamped) compared with dogs with a normal iCa concentration (clamped). Five groups of dogs were studied: control, metabolic (clamped and nonclamped), and respiratory (clamped and nonclamped) acidosis. Metabolic (HCl infusion) and respiratory (hypoventilation) acidosis was progressively induced during 60 min. In the two clamped groups, iCa was maintained at a normal value with an EDTA infusion. Both metabolic and respiratory acidosis increased (P Ͻ 0.05) iCa values in nonclamped groups. In metabolic acidosis, the increase in iCa was progressive and greater (P Ͻ 0.05) than in respiratory acidosis, in which iCa increased by 0.04 mM and then remained constant despite further pH reductions. The increase in PTH values was greater (P Ͻ 0.05) in clamped than in nonclamped groups (metabolic and respiratory acidosis). In the nonclamped metabolic acidosis group, PTH values first increased and then decreased from peak values when iCa increased by Ͼ0.1 mM. In the nonclamped respiratory acidosis group, PTH values exceeded (P Ͻ 0.05) baseline values only after iCa values stopped increasing at a pH of 7.30. For the same increase in iCa in the nonclamped groups, PTH values increased more in metabolic acidosis. In conclusion, 1) both metabolic acidosis and respiratory acidosis stimulate PTH secretion; 2) the physiological increase in the iCa concentration during the induction of metabolic and respiratory acidosis reduces the magnitude of the PTH increase; 3) in metabolic acidosis, the increase in the iCa concentration can be of sufficient magnitude to reverse the increase in PTH values; and 4) for the same degree of acidosis-induced hypercalcemia, the increase in PTH values is greater in metabolic than in respiratory acidosis.hypercalcemia; metabolic acidosis; parathyroid hormone; respiratory acidosis BESIDES ITS WELL-KNOWN EFFECT on calcium homeostasis, parathyroid hormone (PTH) has also been associated with changes in the acid-base status. In 1970, Wills (26) suggested that PTH-induced bone resorption mobilized phosphate to act as a buffer to neutralize acidosis. In subsequent studies, PTH administration has been shown to increase net acid excretion (14, 24) and induce metabolic alkalosis in dogs and humans by both renal and extrarenal mechanisms (15-17). Because PTH appears to have a role in acid-base homeostasis, it would seem reasonable that acid-base disorders may...

Chronic metabolic acidosis stimulated transcellular and solvent drag-induced calcium transport in the duodenum of female rats

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Measuring Total Blood Calcium Displays a Low Sensitivity for the Diagnosis of Hypercalcemia in Incident Renal Transplant Recipients

“…Acidosis induces an increase in PTH secretion (27), probably as a result of a decreased calcium sensing of the parathyroid cells (28). Animal data indicate that the acidosis-induced increase of iCa attenuates but does not eliminate the increase of PTH secretion (29). Consistent with these data, we observed an association between high PTH and low bicarbonate, independent from iCa (data not shown).…”

Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism

“…These in vitro data are consistent with observations that metabolic acidosis is associated with increased serum PTH and calcium levels and that alkalosis suppresses serum PTH in vivo. 4,[6][7][8] The current findings suggest a CaR-based mechanism for these previous data from animal studies. It will be interesting therefore to determine therefore whether acidosis and/or alkalosis elicit chronic changes in PTH secretion in vivo.…”

“…In animal experiments, induction of metabolic acidosis results in increased serum PTH levels and hypercalcemia, whereas induction of alkalosis suppresses serum PTH levels. [4][5][6][7][8] Therefore, because acidosis has been associated with increased serum PTH levels in vivo, we examined whether much smaller, pathophysiologically relevant changes in pH o (60.2) can alter the Ca 2+ o sensitivity of CaR-mediated signaling pathways in HEK-293 cells and whether such effects can be replicated in parathyroid cells. We also examined whether a specific histidine or free cysteine residue could account for CaR pH o sensitivity and, finally, considered the effect of such pathophysiologic changes in pH o on PTH secretion.…”