Effects of the Calcium Ionophore A23187 on Dispersed Bovine Parathyroid Cells

Abstract

Dispersed bovine parathyroid cells were employed to assess the effects of the divalent cation ionophore A23187 on parathyroid function. In the presence of ionophore, both basal parathyroid hormone (PTH) release and isoproterenol-stimulated cAMP accumulation were inhibited by significantly lower concentrations of calcium (half-maximal inhibition at 0.7–0.8 mmvs. 1.0 mm and 1.3–1.4 vs. 1.7–2.0 mm calcium, respectively). After preincubation with ionophore, there was also an alteration in the relationship between agonist-stimulated cAMP accumulation and PTH release similar to that observed previously with elevated extracellular calcium concentrations; with A23187, a given increase in secretion rate was associated with nearly a 10-fold greater increase in cAMP accumulation. A23187 effected a highly significant increase in the rate of efflux of ⁴⁵Ca from dispersed cells. The uptake of ⁴⁵Ca, in contrast, was decreased slightly by ionophore. A predominant effect of ionophore on calcium efflux was also suggested by a significant reduction in cellular ⁴⁵Ca after the addition of A23187 to cells at apparent equilibrium with calcium in the medium. The present results support the hypothesis that alterations in intracellular calcium concentration play a role in the inhibitory effects of medium calcium on 1) basal PTH release, 2) agonist-stimulated cAMP accumulation, and 3) the relationship of agonist-stimulated secretion to cAMP accumulation. Direct studies of ⁴⁵Ca uptake and efflux, however, suggest that the effect of A23187 on these parameters results predominantly from mobilization of intracellular calcium stores rather than influx of extracellular calcium. (Endocrinology106: 133, 1980)