Relationship of 3′,5′-Adenosine Monophosphate Accumulation to Parathyroid Hormone Release in Dispersed Cells from Pathological Human Parathyroid Tissue*

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Abstract
We studied the effects of calcium on cellular cAMP and parathyroid hormone (PTH) release in dispersed parathyroid cells from patients with primary hyperparathyroidism. In four cell preparations there was a statistically significant relationship between calcium-induced changes in these two variables. In three others there was no such correlation. In two of these cAMP content was decreased more than PTH release at high calcium concentrations (2–3 mM) (45% and 85% us. 0%and 30% respectively). In a third PTH release was inhibited 30% or more without any change in cAMP levels. The relationships between basal and agonist-stimulated cAMP accumulation and hormone release were also complex. In three cases, there was a good agreement between the concentration of calcium-inhibiting isoproterenol-stimulated cAMP content and PTH release. On the other hand, in one of these cases and in an additional one there was no clear relationship between the effects of calcium on basal and agonist-stimulated cAMP accumulation. There likewise was not a uniform response to the divalent cation ionophore A23187, which is thought to increase cytosolic calcium concentration. In three preparations of cells with 50% or greater suppression of PTH release by calcium A23187 lowered the concentration of calcium causing half of the maximal inhibition of PTH release. In contrast, three cell preparations with less than 20% suppression of secretion showed no effect of A23187 on the regulation of PTH release by calcium. These results show considerable heterogeneity in the effects of calcium on cAMP accumulation and PTH secretion in pathological parathyroid tissue. Primary hyperparathyroidism might, therefore, be caused by several distinct defects in the regulation of cAMP metabolism and PTH secretion. Alternatively, a single defect might express itself in a number of different ways. The specific derangement(s) in primary hyperparathyroidism and the pathophysiological role of cAMP-dependent and -independent secretory pathways in this disorder remain to be defined.