George S R, Watanabe M, Di Paolo T, Falardeau P, Labrie F, Seeman P
Endocrinology. 1985 Aug;117(2):690-7. doi: 10.1210/endo-117-2-690.
In order to determine whether the high affinity state or the low affinity state of the dopamine receptor mediated the inhibition of release of PRL 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 two phases: one 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 constants (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. These data suggest that the high affinity state of the D2 dopamine receptor is the functional state which mediates the inhibition of PRL release.
为了确定多巴胺受体的高亲和力状态还是低亲和力状态介导了多巴胺激动剂对催乳素释放的抑制作用，测试了大量多巴胺能激动剂（n = 31）和拮抗剂（n = 24）抑制[3H]螺哌隆与猪垂体前叶组织结合的能力，以及它们影响培养的大鼠垂体前叶细胞释放催乳素的能力。所有激动剂（除溴隐亭、麦角隐亭和二氢麦角隐亭外）均以两个阶段抑制[3H]螺哌隆结合：一个阶段发生在纳摩尔或亚纳摩尔浓度（代表多巴胺受体的高亲和力状态），另一个阶段发生在激动剂浓度高得多时（多巴胺受体的低亲和力状态）。每种药物在每种状态下的解离常数（K）通过计算机程序LIGAND得出。观察到高亲和力状态下激动剂的K值与抑制催乳素释放的激动剂浓度几乎相同；低亲和力状态下的K值约高2个数量级。这些数据表明，D2多巴胺受体的高亲和力状态是介导催乳素释放抑制的功能状态。
