Pharmacological and functional characterization of D2, D3 and D4 dopamine receptors in fibroblast and dopaminergic cell lines.
Pharmacological and functional characterization of D2, D3 and D4 dopamine receptors in fibroblast and dopaminergic cell lines.
复制标题
DOI：
--
复制
发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Lei Tang;Richard D. Todd;A. Heller;Karen L. O'Malley
中科院分区：
文献类型：
--
作者：
Lei Tang;Richard D. Todd;A. Heller;Karen L. O'Malley
为了研究D2样多巴胺受体的特性，将D2、D3和D4克隆转染小鼠Ltk-成纤维细胞CCL1.3和神经元中脑细胞系MN9D。大多数衍生的拮抗剂和激动剂的抑制常数是相同的给定受体在两种细胞系的饱和和竞争结合实验确定。拮抗剂的效价顺序为：eticlopride， D2 > D3 > D4；m -09151-2, d2 = d4 > d3；spiperone, D2 = D3 > D4；（+）-丁他卡莫，D2 > D3 > D4；氯氮平，D4 > D2 > D3；对于激动剂，喹匹罗，D3 = D4 > D2；7-羟基-2-（二正丙基）-氨基四乙胺，D3 > D2 = D4。在功能上，D2刺激增加了CCL1.3细胞的肌醇磷酸水平，而在MN9D细胞中没有，而D2激活抑制了福斯克林刺激的两种细胞系的环AMP水平。D4刺激对两种细胞类型的肌醇磷酸代谢均无影响，但在MN9D细胞中抑制腺苷酸环化酶。D2和D4介导的环AMP降低均可通过百日咳毒素预孵育阻断。D3在两种细胞系中都不与这些途径结合。逆转录/聚合酶链反应技术用于确定细胞信号系统的可用性。CCL1.3和MN9D细胞均有高水平的G α i2表达，而细胞均不表达G α i1或G α i3。这些数据表明，在两种细胞系中，D2受体与G α i2亚型偶联，而D4则不偶联。（摘要删节250字）
In order to study the properties of the D2-like dopamine receptors, D2, D3 and D4 clones were transfected into mouse Ltk- fibroblasts, CCL1.3, and a neuronal mesencephalic cell line, MN9D. Most of the derived antagonist and agonist inhibition constants were the same for a given receptor in either cell line as determined by saturation and competition binding experiments. The rank order potencies for antagonists are: eticlopride, D2 > D3 > D4; YM-09151-2, D2 = D4 > D3; spiperone, D2 = D3 > D4; (+)-butaclamol, D2 > D3 > D4; clozapine, D4 > D2 > D3; and for agonists, quinpirole, D3 = D4 > D2; 7-hydroxy-2-(di-n-propyl)-aminotetralin, D3 > D2 = D4. Functionally, D2 stimulation increases inositol phosphate levels in CCL1.3 cells but not in MN9D, whereas D2 activation inhibits forskolin-stimulated cyclic AMP levels in both cell lines. D4 stimulation has no effect on inositol phosphate metabolism in either cell type, but inhibits adenylate cyclase in MN9D cells. Both the D2 and D4 mediated decreases in cyclic AMP can be blocked by preincubation with pertussis toxin. D3 does not couple to these pathways in either cell line. Reverse transcription/polymerase chain reaction techniques were used to determine the availability of cellular signalling systems. Both CCL1.3 and MN9D cells have high levels of G alpha i2 expression, whereas neither cell expresses G alpha i1 or G alpha i3. These data imply that the D2 receptor couples to the G alpha i2 subtype in both cell lines, whereas D4 does not.(ABSTRACT TRUNCATED AT 250 WORDS)