Inhibitory effects of hypermagnesemia on the renal action of parathyroid hormone (PTH)

Available evidence indicates that serum magnesium (Mg⁺⁺) levels influence the secretion rate of PTH. Whether serum Mg⁺⁺ concentrations also modify the action of PTH on its target organs has not been established. The present experiments were designed to study this possibility. The effect of infusing PTH on the urinary excretion of cyclic AMP (cAMP) and PO was examined in 5 normal dogs at 2 different levels of serum Mg⁺⁺. At normal serum Mg⁺⁺ concentrations (1.85 ± .13 mg%) PTH infusion increased cAMP excretion from 1.84 ± .18 to 4.16 ± 1.03 nMoles/min and fractional PO₄ = excretion (FE(PO₄)) from 2.1 ± .7% to 26.8 ± 3.7%. When an identical amount of PTH was given to the same dogs at a serum Mg⁺⁺ of 4.28 ± .27 mg%, FE(PO₄) increased to only 7.7 ± 2.5% and cAMP excretion remained unchanged (1.45 ± .16 vs 1.63 ± .63 nMoles/min). Identical results were obtained in PTX dogs with a mean serum Mg⁺⁺ of 4.9 ± .15 mg%. Increased serum Mg⁺⁺ levels had no effect on the the phosphaturia produced by the infusion of dibutyryl cAMP to PTX dogs. In vitro studies, using rat renal cortical slices, revealed a progressive decrease in cAMP production in responses to PTH as the Mg⁺⁺ concentrations were increased in the incubation medium. The overall results indicate that hypermagnesemia inhibits the phosphaturic response to PTH by decreasing the renal production of cAMP. Hypermagnesemia therefore, not only decreases PTH secretion but it also inhibits the peripheral action of the hormone.