![]() |
|
|
Molecular Pharmacology, Vol 18, 335-340, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics
1 Endocrine-Hypertension Unit, Department of Medicine, Peter Bent Brigham Hospital, Boston, Massachusetts 02115
2 Metabolic Diseases Branch, NIAMDD, NIH, Bethesda, Maryland 20205
3 Experimental Therapeutics Branch, NINCDS, NIH, Bethesda, Maryland
20205
Several dopaminergic ligands were assessed for their effects on cAMP accumulation,
adenylate cyclase activity, and parathyroid hormone (PTH) release from dispersed bovine
parathyroid cells. Dopamine, 6,7-dihydroxy-1,2,3,4 tetrahydronaphthalene (ADTN),
2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (SKF-38393), and apomorphine increased cAMP content 30-, 25-, 10-, and 2- to 3-fold with Kas of 0.6, 0.5, 1, and 1-3 µM, respectively. These same agents also stimulated adenylate cyclase activity up to 4-fold and PTH release 1.3- to 3-fold. With the exception of lisuride (Ki = 15 nM), ergot
derivatives were of relatively low potency (Kis = 0.4-20 µM) in inhibiting dopamine-stimulated cAMP accumulation. Similar Kis were observed for effects on dopamine-stimulated adenylate cyclase activity and PTH release. Interactions of these ligands with
the dopamine receptor could be clearly differentiated from effects of
-adrenergic or
-adrenergic receptors also known to modulate cAMP accumulation and secretion in this
cell type. These results demonstrate the presence of a D-1 dopaminergic receptor on
bovine parathyroid cells and document further the relationship in this receptor subclass
between adenylate cyclase activity, cAMP accumulation, and a biologic response.