Prostaglandin F2αandα-Adrenergic Agonists Regulate Parathyroid Cell Function via the Inhibitory Guanine Nucleotide Regulatory Protein

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Abstract
Prostaglandin F2.alpha. (PGF2.alpha.) and .alpha.-adrenergic agonists inhibit cAMP production and PTH secretion in dispersed bovine parathyroid cells. We have tested the mechanism of these effects utilizing pertussis toxin which catalyzes ADP ribosylation and inactivation of the inhibitory adenylate cyclase coupling protein Ni. Dispersed bovine parathyroid cells treated with or without 0.5 .mu.g/ml pertussis toxin were tested with stimulatory (epinephrine, isoproterenol) or inhibitory (PGF2.alpha.) agonists for responses in cAMP accumulation (5-min incubation) or PTH (90-min incubation) release. Pertussis toxin produced an enhanced response to epinephrine (a mixed .alpha.-adrenergic and .beta.-adrenergic agonist) in cAMP production and in PTH secretion. PGE2.alpha. inhibited intracellular cAMP by 40% and PTH secretion by 35%. Pertussis toxin treatment of bovine parathyroid cells reduced the PGF2.alpha. inhibition. We conclude that: 1) inhibition of PTH release by PGF2.alpha. and .alpha.-adrenergic agonists parallels inhibition of cAMP production; 2) pertussis toxin blocks the inhibitory actions of PGF2.alpha. and .alpha.-adrenergic agents on cAMP accumulation and PTH secretion; 3) the inhibitory coupling protein Ni mediates the inhibitory effects of these agents.
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