HOMOLOGOUS DESENSITIZATION OF THE D1 DOPAMINE RECEPTOR
HOMOLOGOUS DESENSITIZATION OF THE D1 DOPAMINE RECEPTOR
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DOI：
10.1111/j.1471-4159.1990.tb05803.x
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发表时间：
1990-12-01
影响因子：
4.7
通讯作者：
BALL, SG
中科院分区：
文献类型：
--
作者：
BALMFORTH, AJ;WARBURTON, P;BALL, SG
预孵育的D384细胞，来自人类星形细胞瘤细胞系G-CCM，多巴胺导致在一个时间依赖性衰减环AMP响应随后多巴胺刺激。这种效应是激动剂特异性的，因为前列腺素E1（PGE 1）刺激类似处理的细胞的环AMP保持不变。多巴胺的衰减是浓度依赖性的，在100 μ m处观察到最大值。多巴胺浓度-反应曲线的控制和多巴胺预孵育的细胞的比较显示没有变化的Ka表观值，但显着衰减的最大反应。预孵育的细胞与多巴胺在D1的存在下，但不是D2的选择性拮抗剂部分防止所观察到的衰减。多巴胺反应性的衰减，也得到了D384细胞与D1，但不是D2受体激动剂预孵育。达到的衰减水平与刺激环AMP的激动剂效率相关：SKF 38393 <3，4-二羟基诺米芬辛<非诺多泮< 2-氨基-6，7-二羟基-1，2，3，4-四氢萘=多巴胺。然而，使用添加低浓度毛喉素的协同效应，增加3，4-二羟基诺米芬新刺激环AMP的效率，在随后对多巴胺的反应的衰减中没有产生进一步的变化。因此，由D384细胞表达的D1多巴胺受体经历同源脱敏。D1多巴胺受体的解偶联似乎不依赖于环AMP的形成，类似于β-AMP的提出的机制。肾上腺素能受体
Preincubation of D384 cells, derived from the human astrocytoma cell line G-CCM, with dopamine resulted in a time-dependent attenuation of cyclic AMP responsiveness to subsequent dopamine stimulation. This effect was agonist specific because the prostaglandin E1 (PGE1) stimulation of cyclic AMP of similarly treated cells remained unchanged. The attenuation by dopamine was concentration dependent with a maximum observed at 100 .MU.m. A comparison of dopamine concentration-response curves of control and dopamine-preincubated cells revealed no change in the Ka apparent value, but a marked attenuation of the maximal response. Preincubation of cells with dopamine in the presence of D1 but not D2 selective antagonists partially prevented the observed attenuation. Attenuations in dopamine responsiveness were also obtained when D384 cells were preincubated with D1 but not D2 receptor agonists. The level of attenuation attained related to agonist efficiency in stimulating cyclic AMP: SKF38393 < 3,4-dihydroxynomifensine < fenoldopam < 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene = dopamine. However, increasing the efficiency of 3,4-dihydroxynomifensine stimulation of cyclic AMP, using the synergistic effect of adding a low concentration of forskolin, produced no further change in the attenuation of the subsequent response to dopamine. Thus, the D1 dopamine receptors expressed by D384 cells undergo homologous desensitization. Uncoupling of the D1 dopamine receptor appears to be independent of cyclic AMP formation, analogous to a mechanism proposed for the .beta.-adrenergic receptor.