Prosser R A, McArthur A J, Gillette M U
University of Illinois at Urbana-Champaign 61801.
Proc Natl Acad Sci U S A. 1989 Sep;86(17):6812-5. doi: 10.1073/pnas.86.17.6812.
The suprachiasmatic nuclei (SCN) of mammals contain a circadian clock that synchronizes behavioral and physiological rhythms to the daily cycle of light and darkness. We have been probing the biochemical substrates of this endogenous pacemaker by examining the ability of treatments affecting cyclic nucleotide-dependent pathways to induce changes in the phase of oscillation in electrical activity of rat SCN isolated in brain slices. Our previous work has shown that daytime treatments that stimulate cAMP-dependent pathways induce phase shifts of the SCN pacemaker in vitro but treatments during the subjective night are without effect. In this study we report that the phase of SCN oscillation is reset by treatments that stimulate cGMP-dependent pathways, but only during the subjective night. Thus, the nocturnal period of SCN sensitivity to cGMP is in antiphase to the diurnal period of sensitivity to cAMP. These results suggest that cAMP and cGMP affect the SCN pacemaker through separate biochemical pathways intrinsic to the SCN. These studies provide evidence that changing biochemical substrates within the SCN circadian clock may underlie some aspects of differential temporal sensitivity of mammals to resetting stimuli.
哺乳动物的视交叉上核（SCN）含有一个昼夜节律时钟，可使行为和生理节律与昼夜明暗循环同步。我们一直在通过研究影响环核苷酸依赖性途径的处理方法诱导离体脑片大鼠SCN电活动振荡相位变化的能力，来探究这个内源性起搏器的生化底物。我们之前的研究表明，白天刺激cAMP依赖性途径的处理可在体外诱导SCN起搏器的相位变化，但在主观夜间进行的处理则没有效果。在本研究中，我们报告称，刺激cGMP依赖性途径的处理可重置SCN振荡的相位，但仅在主观夜间有效。因此，SCN对cGMP敏感的夜间时段与对cAMP敏感的白天时段呈反相。这些结果表明，cAMP和cGMP通过SCN固有的不同生化途径影响SCN起搏器。这些研究提供了证据，表明SCN昼夜节律时钟内生化底物的变化可能是哺乳动物对重置刺激的不同时间敏感性某些方面的基础。
