Mechanism for shifting the phase of a circadian rhythm by serotonin: involvement of cAMP.
Mechanism for shifting the phase of a circadian rhythm by serotonin: involvement of cAMP.
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DOI：
10.1073/pnas.79.2.660
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发表时间：
1982
影响因子：
11.1
通讯作者：
A. Eskin;G. Corrent;C. -. Lin;D. McAdoo
中科院分区：
文献类型：
--
作者：
A. Eskin;G. Corrent;C. -. Lin;D. McAdoo
5-羟色胺(5-羟色胺，5-羟色胺)改变了海兔眼睛的昼夜节律的相位。我们研究了cAMP在调节5-羟色胺对节律的影响中的作用。5-羟色胺产生的相移被应该增加细胞内cAMP水平的处理所模仿。CAMP-8-苯硫基-cAMP的类似物，在5-羟色胺对节律有类似影响的各时相中，提前和延迟节律。此外，两种磷酸二酯酶抑制剂Ro-20-1724和罂粟碱引起了提前的相移，而5-羟色胺则使节律提前。磷酸二酯酶抑制剂Ro-20-1724和3-异丁基-1-甲基黄嘌呤分别增强阈值以下剂量5-羟色胺对节律的影响。5-羟色胺和8-苯硫基-cAMP对节律的影响是非相加的，说明5-羟色胺和8-苄硫基-cAMP通过共同的途径影响节律。最后，5-羟色胺使眼睛中的cAMP水平发生了很大的变化(13倍)。这些结果表明，cAMP介导了5-羟色胺对节律的影响。CAMP在昼夜节律系统中有两种可能的作用。CAMP系统要么是携带途径中的细胞内步骤，要么是生物时钟的一部分。由于5-羟色胺、8-苄硫基-cAMP和三种磷酸二酯酶抑制剂抑制眼睛的冲动，cAMP也可能介导5-羟色胺产生的抑制作用，或者它可能参与调节全天自发冲动的频率。
Serotonin (5-hydroxytryptamine, 5-HT) shifts the phase of the circadian rhythm in the eye of Aplysia. We have examined the role of cAMP in mediating the effects of 5-HT on the rhythm. The phase shifts produced by 5-HT are mimicked by treatments that should increase intracellular levels of cAMP. An analogue of cAMP-8-benzylthio-cAMP, advanced and delayed the rhythm at phases in which 5-HT had similar effects on the rhythm. In addition, two phosphodiesterase inhibitors, Ro-20-1724 and papaverine, caused advance phase shifts where 5-HT advances the rhythm. The phosphodiesterase inhibitors Ro-20-1724 and 3-isobutyl-1-methylxanthine each potentiated the effect of subthreshold doses of 5-HT on the rhythm. The effects of 5-HT and 8-benzylthio-cAMP on the rhythm were nonadditive, indicating that 5-HT and 8-benzylthio-cAMP affect the rhythm through a common pathway. Finally, 5-HT produced large changes (13-fold) in the levels of cAMP in the eye. These results indicate that cAMP mediates the effect of 5-HT on the rhythm. There are two possible roles for cAMP in the circadian system. Either the cAMP system is an intracellular step in an entrainment pathway or it is part of the biological clock. Because 5-HT, 8-benzylthio-cAMP, and three phosphodiesterase inhibitors inhibit impulses from the eye, cAMP may also mediate the inhibition produced by 5-HT, or it might be involved in regulating the frequency of spontaneous impulses throughout the day.