Abstract：
Dopamine D2 receptors (D2Rs) play crucial roles in regulating diverse physiological functions of the central nervous system and peripheral organs. D2Rs are also expressed in mammary glands. However, which cell types express D2Rs and whether they are involved in milk production remains unclear. The present findings revealed that D2Rs are expressed in the apical regions of the lateral membranes of mammary epithelial cells (MECs) in lactating mice. We also investigated the effects of the D2R agonist bromocriptine and/or antagonist domperidone on intracellular cAMP levels, milk protein production, and apoptosis in a lactation culture model of MECs that produce major milk components like lactating MECs in vivo. We found that bromocriptine decreased intracellular cAMP levels, whereas domperidone dose-dependently neutralized this effect. Bromocriptine also inhibited casein and lactoferrin production and suppressed activities of STAT5 and glucocorticoid receptors (GRs). Domperidone neutralized the inhibition of casein production as well as STAT5 and GR inactivation induced by bromocriptine. Furthermore, D2R activation by bromocriptine induced apoptosis and inactivated ERK, a signaling molecule responsible for promoting cell proliferation and survival. Domperidone attenuated ERK inactivation and apoptosis induced by bromocriptine. These findings suggest that D2Rs play regulatory roles in milk protein production and apoptosis in MECs.
摘要：
多巴胺D2受体（D2R）在调节中枢神经系统和外周器官的多种生理功能中起着至关重要的作用。D2R也在乳腺中表达。然而,哪些细胞类型表达D2R，以及它们是否参与牛奶生产尚不清楚。本发现表明，D2R在泌乳小鼠的乳腺上皮细胞（MEC）的侧膜的顶端区域表达。我们还研究了D2R激动剂溴隐亭和/或拮抗剂多潘立酮对细胞内cAMP水平的影响，牛奶蛋白质生产，和在体内产生主要乳成分如泌乳MECs的MECs的泌乳培养模型中的细胞凋亡。我们发现溴隐亭降低细胞内cAMP水平,而多潘立酮剂量依赖性地中和了这种作用。溴隐亭还抑制酪蛋白和乳铁蛋白的产生，并抑制STAT5和糖皮质激素受体（GR）的活性。多潘立酮中和了溴隐亭诱导的酪蛋白产生抑制以及STAT5和GR失活。此外，溴隐亭激活D2R诱导的细胞凋亡和失活的ERK，负责促进细胞增殖和存活的信号分子。多潘立酮减弱溴隐亭诱导的ERK失活和凋亡。这些发现表明D2R在MECs的乳蛋白产生和细胞凋亡中起调节作用。
