FUNCTIONAL INTERACTION OF MELATONIN RECEPTORS AND D1 DOPAMINE-RECEPTORS IN CULTURED CHICK RETINAL NEURONS
FUNCTIONAL INTERACTION OF MELATONIN RECEPTORS AND D1 DOPAMINE-RECEPTORS IN CULTURED CHICK RETINAL NEURONS
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DOI：
10.1523/jneurosci.15-03-02179.1995
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发表时间：
1995-03-01
影响因子：
5.3
通讯作者：
GAN, JW
中科院分区：
文献类型：
--
作者：
IUVONE, PM;GAN, JW
在从胚胎第 8 天鸡视网膜制备并培养 6 天的神经细胞中研究了褪黑激素受体和 D1 多巴胺受体可能的相互作用。多巴胺刺激培养的视网膜细胞中 cAMP 的积累。多巴胺的这种作用可通过添加多巴胺受体拮抗剂（氟哌啶醇和 SCH23390）或褪黑激素受体激动剂（褪黑激素、2-碘褪黑激素和 6-氯褪黑激素）来拮抗。褪黑激素对多巴胺刺激的 cAMP 积累的抑制是浓度依赖性的，在大约 160 pM 时具有半最大抑制。褪黑激素在所有多巴胺浓度下都能抑制多巴胺的作用，将神经递质的最大反应抑制约 70%。褪黑激素还抑制 SKF 82958（一种选择性 D1 多巴胺受体激动剂）对 cAMP 积累的刺激。用百日咳毒素预处理培养物对多巴胺刺激的 cAMP 积累没有显着影响，但抑制了对褪黑激素的反应。与它对 cAMP 积累的影响相反，褪黑激素对多巴胺刺激的磷酸肌醇积累没有影响。这些结果表明，褪黑激素受体通过抑制性 G 蛋白与多巴胺受体调节的腺苷酸环化酶偶联，并证明了除了抑制多巴胺释放之外的另一种机制，通过该机制褪黑激素可以调节多巴胺能 神经传递。
The possible interaction of melatonin receptors and D1 dopamine receptors was investigated in neural cells prepared from embryonic day 8 chick retinas and cultured for 6 d. Dopamine stimulated cAMP accumulation in cultured retinal cells. This effect of dopamine was antagonized by addition of dopamine receptor antagonists (haloperidol and SCH23390) or melatonin receptor agonists (melatonin, 2-iodomelatonin, and 6-chloromelatonin). The inhibition of dopamine-stimulated cAMP accumulation by melatonin was concentration dependent, with half-maximal inhibition at approximately 160 pM. Melatonin inhibited the effect of dopamine at all dopamine concentrations, suppressing the maximal response to the neurotransmitter by approximately 70%. Melatonin also inhibited the stimulation of cAMP accumulation by SKF 82958, a selective D1 dopamine receptor agonist. Pretreatment of cultures with pertussis toxin had no significant effect on dopamine-stimulated cAMP accumulation, but inhibited the response to melatonin. In contrast to its effect on cAMP accumulation, melatonin had no effect on dopamine-stimulated inositol phosphate accumulation, These results suggest that melatonin receptors are coupled to dopamine receptor-regulated adenylate cyclase via an inhibitory G protein, and demonstrate another mechanism, in addition to inhibition of dopamine release, through which melatonin can modulate dopaminergic neurotransmission.