alpha-Adrenergic inhibition of adenosine 3',5'-monophosphate accumulation and parathyroid hormone release from dispersed bovine parathyroid cells.
The possibility of alpha-adrenergic modulation of cAMP 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 calcium concentration. Stimulation of PTH release by (-)epinephrine and (-)norepinephrine was potentiated by phentolamine and inhibited by the beta-adrenergic blocker, (-)propranolol, demonstrating alpha-adrenergic modulation of hormone release and confirming the close relationship between cAMP accumulation and PTH release previously shown in this system. These results demonstrate the presence of an alpha-adrenergic receptor in dispersed bovine parathyroid cells which inhibits agonist-stimulated cAMP accumulation and PTH release by a mechanism independent of extracellular calcium.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D010281:Parathyroid Hormone; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine