Characterization of the Dopamine-Responsive Adenylate Cyclase of Bovine Parathyroid Cells and Its Relationship to Parathyroid Hormone Secretion

To investigate further the mechanism of dopamine (DA)-stimulated parathyroid hormone (PTH) secretion, we have identified and studied DA-sensitive adenylate cyclase in a particulate preparation of osmotically lysed dispersed bovine parathyroid cells. Adenylate cyclase was responsive to DA at concentrations as low as 0.3 μM, and the maximal stimulation in the presence of GTP was 2- to 4-fold that of activity with GTP alone. (-)Propranolol (1 μM) abolished the stimulation by (-)isoproterenol but did not inhibit the DA-stimulated adenylate cyclase, whereas a-flupenthixol (1 μM) inhibited DA stimulation but not that of (-)isoproterenol. The dopaminergic agonists epinine and BJ-dihydroxy-l,2,3,4-tetrahydronaphthalene were nearly as effective as DA in stimulating the enzyme, while apomorphine displayed partial agonist activity. The dopaminergic antagonists chlorpromazine, fluphenazine, and haloperidol inhibited the DA-stimulated adenylate cyclase. There was a close correspondence between the Ka values for DA and...