α-Adrenergic Inhibition of Adenosine 3′,5′-Monophosphate Accumulation and Parathyroid Hormone Release from Dispersed Bovine Parathyroid Cells*

Abstract

The possibility of .alpha.-adrenergic modulation of c[cyclic]AMP accumulation and parathyroid hormone (PTH) release was investigated in dispersed bovine parathyroid cells. cAMP accumulation due to the mixed .alpha.- and .beta.-adrenergic agonists, (-)epinephrine and (-)norepinephrine, was significantly enhanced by the .alpha.-adrenergic inhibitor phentolamine; that due to the pure .beta.-adrenergic agonist, (-)isoproterenol, was not altered significantly. Direct inhibition of agonist-stimulated cAMP accumulation was effected by adding increasing concentrations of (-)epinephrine to concentrations of (-)isoproterenol maximally stimulating cAMP accumulation. A 50-75% inhibition of cAMP was observed which was specifically blocked by phentolamine. This inhibition was not specific for .beta.-adrenergic stimulation, as (-)epinephrine also inhibited dopamine-stimulated cAMP accumulation. The inhibition of (-)isoproterenol-stimulated cAMP accumulation by (-)epinephrine was unaffected by ambient Ca concentration. Stimulation of PTH release by (-)epinephrine and (-)norepinephrine was potentiated by phentolamine and inhibited by the .beta.-adrenergic blocker, (-)propranolol, apparently demonstrating .alpha.-adrenergic modulation of hormone release and confirming the close relationship between cAMP accumulation and PTH release previously shown in this system. Apparently there is an .alpha.-adrenergic receptor in dispersed bovine parathyroid cells which inhibits agonist-stimulated cAMP accumulation and PTH release by a mechanism independent of extracellular Ca.