Magnesium Promotes Both Parathyroid Hormone Secretion and Adenosine 3′,5′-Monophosphate Production in Rat Parathyroid Tissues and Reverses the Inhibitory Effects of Calcium on Adenylate Cyclase*

Abstract

Reduced extracellular Ca2+ is known to promote PTH secretion, while severe Mg2+ depletion has the opposite effect. We have correlated the effects of Mg2+ and Ca2+ on parathyroid hormone (PTH) secretion and cAMP accumulation by rat parathyroid tissues in vitro with the effects of these two metals on adenylate cyclase activity in broken membrane preparations. PTH secretion was maximal at 0.5 mM Ca2+, falling to low levels as the Ca2+ concentration was increased to 2.5 mM. Deletion of Mg2+ from the medium resulted in a marked decrease in PTH secretion at any given Ca2+ concentration. At a constant Ca2+ concentration of 1 mM, both PTH secretion and cAMP production rose to maximal rates as the Mg2+ concentration was increased from 0 to 2 mM. The adenylate cyclase of rat parathyroid membranes was stimulated by both GTP and guanyl-5'-yl-imidodiphosphate [Gpp(NH)p]. EDTA-treated membranes could not be stimulated by Gpp(NH)p. Repletion with Mg2+ was more effective than repletion with Ca2+ in restoring responsiveness to the guanine nucleotide. When membranes were maximally preactivated by Gpp(NH)p and then assayed in the presence of variable concentrations of metal ions, enzyme activity was directly inhibited by Ca2+ and stimulated by Mg2+. Adenylate cyclase sensitivity to Ca2+ inhibition was dependent upon the Mg2+ concentration; in the presence of 0.6 mM Mg2+ a 50% inhibition was produced by 0.05 mM Ca2+, while in the presence of 8 mM Mg2+ a 10-fold higher Ca2+ concentration was required for a similar inhibitory effect. The results suggest that Ca2+ may decrease PTH secretion at least in part by a direct inhibition of adenylate cyclase. Mg2+ may promote PTH secretion either by enhancing the activation of adenylate cyclase by endogenous guanine nucleotides or by competing with Ca2+ for binding to a distinct regulatory site on the enzyme.

Magnesium deprivation inhibits the expression of differentiation‐related phenotypes in human promyelocytic leukemia HL‐60 cells

“…Magnesium specifically regulates adenylate cyclase activity in numerous cells and species (Cech et al, 1980) and enhances insulin-dependent stimulation of cyclic AMP phosphodiesterase in adipocytes (Ueda et al, 1984). Magnesium also promotes the secretion of parathyroid hormone and the activity o f cyclic AMP in rat parathyroid tissues (Mahaffee et al, 1982 there are few reports on the role of magnesium ions in cell differentiation.In the present study, we investigated the effect of magnesium deprivation o n human promyelocytic leukemia HL-60 cell differentiation. Firstly, we showed that a reduction in HL-60 extracellular magnesium decreased the intracellular magnesium content and that this deprivation inhibited not only their proliferation but also differentiation induced by various compounds such as 1a,25 dihydroxyvitamine D3 (1,25(OHjzD32), 0-all-trans retinoic acid CRA), 12-o-tetradecanoyl phorbol-13-acetate (TPA), dimethylsulfoxide (DMSO), and acla-…”

Effect of Magnesium Infusion on Calcium Handling in the Rat Kidney

“…Thus an increased plasma magnesium would reduce PTH secretion and so reduce distal reabsorption of calcium. While this is theoretically possible in our studies we regard it as unlikely because PTH secretion is less sensitive to ionic magnesium than calcium (Habener & Potts, 1976;Mahafee et al 1982). In addition, others have demonstrated, albeit at higher plasma magnesium concentrations than reported here, that magnesium increases calcium excretion even after thyroparathyroidectomy (Clark, 1969;Quamme & Dirks, 1980).…”

“…It might be that magnesium exerts its effects because of its actions on parathyroid hormone (PTH), a hormone which increases calcium reabsorption in the distal parts of the nephron (Habener & Potts, 1976;Brown & Thatcher, 1982;Mahafee, Cooper, Ramp & Ontjes, 1982). Thus an increased plasma magnesium would reduce PTH secretion and so reduce distal reabsorption of calcium.…”

The Effect of Magnesium on the Fine Structure of the Golden Hamster Parathyroid Gland in Vivo and in Vitro

“…On the other hand, Mahaffee et aL (1982) have reported in the in vitro study that Mg promotes PTH secretion either by enhancing the activation of adenylate cyclase by endogenous guanine nucleotides or by competing with calcium for binding to a distinct regulatory site on the enzyme. In addition, there have been only a few morphological studies regarding the effect of Mg on the function of the parathyroid gland (Altenahr and Leonhardt, 1972;Boquist, 1977).…”