The Functional State of the Dopamine Receptor in the Anterior Pituitary Is in the High Affinity Form*

Abstract

To determine whether the high affinity state or the low affinity state of the dopamine receptor mediated the inhibition of release of PRL [prolactin] by dopamine agonists, a large number of dopaminergic agonists (n = 31) and antagonists (n = 24) were tested for their potencies to inhibit the binding of [3H] spiperone to porcine anterior pituitary tissue and for their potencies to affect the release of PRL from rat anterior pituitary cells in culture. All agonists (except bromocriptine, ergocryptine, and dihydroergocryptine) inhibited [3H]spiperone binding in 2 phases: 1 phase occurred at nanomolar or subnanomolar concentrations (representing the high affinity state of the dopamine receptor) and the other phase occurred at much higher concentrations of agonist (the low affinity state of the dopamine receptor). The dissociation constant (K) for each drug at each state were derived by computer, with the program LIGAND. It was observed that the agonist K values for the high affinity state were virtually identical with those agonist concentrations inhibiting PRL release; the K values for the low affinity state were about 2 orders higher. Apparently, the high affinity state of the D2 dopamine receptor is the functional state with mediates the inhibition of PRL release.