Dopaminergic inhibition of adenylate cyclase correlates with high affinity agonist binding to anterior pituitary D2 dopamine receptors.

Journal Article (Journal Article)

Dopamine (DA) and the dopaminergic agonists n-propylnorapomorphine (NPA), 2-amino-6,7-dihydroxytetrahydronaphthalene (ADTN) and apomorphine (APO) inhibit forskolin-stimulated adenylate cyclase activity in a dose-dependent fashion by more than 40% in membrane preparations of the porcine anterior pituitary gland. These agonists exhibit apparent dissociation constants that follow an expected dopaminergic order of potency (NPA greater than ADTN greater than or equal to APO greater than DA). The inhibition is dependent on guanine nucleotides and is reversible by dopaminergic antagonists (spiroperidol greater than (+)-butaclamol much greater than (-)-butaclamol). The potencies of these agonists in inhibiting forskolin-stimulated adenylate cyclase activity correlate with the agonist dissociation constants (KH) for binding to the high affinity receptor state (RH) in porcine anterior pituitary membranes (De Lean et al., Mol. Pharmacol. 1982, 22, 290-297) and the EC50 for inhibition of prolactin release from rat anterior pituitary cells in culture (Caron et al., J. Biol. Chem. 1978, 253, 2244-2253). Furthermore, the intrinsic activities of dopamine and the other agonists for inhibition of forskolin-stimulated adenylate cyclase are similar and correlate well with the ability of these agents to induce a comparable proportion (50%) of the receptor in a high affinity state. Together these data provide additional support for the physiological relevance of the high affinity agonist binding state of the D2 receptor in mediating the decrease in prolactin secretion via attenuation of adenylate cyclase.

Full Text

Duke Authors

Cited Authors

  • McDonald, WM; Sibley, DR; Kilpatrick, BF; Caron, MG

Published Date

  • July 1984

Published In

Volume / Issue

  • 36 / 3

Start / End Page

  • 201 - 209

PubMed ID

  • 6540722

International Standard Serial Number (ISSN)

  • 0303-7207

Digital Object Identifier (DOI)

  • 10.1016/0303-7207(84)90037-6


  • eng

Conference Location

  • Ireland