Eskin A, Corrent G, Lin C Y, McAdoo D J
Proc Natl Acad Sci U S A. 1982 Jan;79(2):660-4. doi: 10.1073/pnas.79.2.660.
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.
血清素（5-羟色胺，5-HT）可改变海兔眼睛昼夜节律的相位。我们研究了环磷酸腺苷（cAMP）在介导5-HT对该节律影响中的作用。5-HT产生的相位变化可被那些应能提高细胞内cAMP水平的处理所模拟。一种cAMP类似物——8-苄硫基-cAMP，在5-HT对节律有类似作用的相位提前和延迟了节律。此外，两种磷酸二酯酶抑制剂，罗-20-1724和罂粟碱，在5-HT使节律提前的情况下也导致了相位提前。磷酸二酯酶抑制剂罗-20-1724和3-异丁基-1-甲基黄嘌呤各自增强了阈下剂量的5-HT对节律的作用。5-HT和8-苄硫基-cAMP对节律的作用并非相加的，这表明5-HT和8-苄硫基-cAMP通过一条共同途径影响节律。最后，5-HT使眼睛中的cAMP水平产生了大幅变化（13倍）。这些结果表明cAMP介导了5-HT对节律的作用。cAMP在昼夜节律系统中有两种可能的作用。要么cAMP系统是同步化途径中的一个细胞内步骤，要么它是生物钟的一部分。由于5-HT、8-苄硫基-cAMP和三种磷酸二酯酶抑制剂抑制了来自眼睛的冲动，cAMP可能还介导了5-HT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。
