Relationship of Intracellular 3′,5′-Adenosine Monophosphate Accumulation to Parathyroid Hormone Release from Dispersed Bovine Parathyroid Cells*

Abstract

The relationship of c[cyclic]AMP accumulation to PTH [parathyroid hormone] release was investigated in dispersed bovine parathyroid cells. Intracellular cAMP was stimulated 3-fold by 2 .times. 10-4 M methylisobutylxanthine, a potent phosphodiesterase inhibitor, and 40- to 60-fold by 10-6 M (-)isoproterenol. Increases in intracellular cAMP were accompanied by release of cAMP into the extracellular space, and this release was inhibited by probenecid. Increased intracellular cAMP in response to (-)isoproterenol was accompanied by a rapid increase in PTH release. Both increased cAMP accumulation and PTH release due to .beta.-adrenergic agonists were rapidly reversed (within 3 min) by (-)propranolol, suggesting that intracellular cAMP regulates the rate of hormone release. The increased rate of PTH release due to a variety of agonists (.beta.-adrenergic, dopaminergic and secretin) was linearly related to the logarithm of the increment in intracellular cAMP. This relationship was independent of the agonist employed and was also true for agents which lowered agonist-stimulated intracellular cAMP and PTH release (.alpha.-adrenergic agonists and prostaglandin F2.alpha.). With increased extracellular Ca concentration, higher intracellular cAMP concentrations were required to achieve a given rate of PTH release. Increased intracellular cAMP alters the rate of hormone release; a close log-linear relationship exists between intracellular cAMP and the rate of PTH release, independent of the nature of the agonist; inhibition of cAMP accumulation due to .alpha.-adrenergic agonists and prostaglandin F2.alpha. can account for the observed decrease in PTH release; and, extracellular Ca alters the response to a given intracellular cAMP concentration.