Harrington M E, Hoque S, Hall A, Golombek D, Biello S
Departments of Psychology and Biological Sciences, Smith College, Northampton, Massachusetts 01063, USA.
J Neurosci. 1999 Aug 1;19(15):6637-42. doi: 10.1523/JNEUROSCI.19-15-06637.1999.
The endogenous circadian pacemaker in mammals is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. Various cues can reset circadian rhythm phase, thereby entraining the internal rhythm to the environmental cycle, and these effects can be investigated using an in vitro method to measure phase shifts of the SCN. Although pituitary adenylate cyclase activating peptide (PACAP) is localized in retinal inputs to the SCN, it has been reported to alter clock phase only during the subjective day (Hannibal et al., 1997), whereas light alters phase only in the subjective night. In this study we show that PACAP can reset the clock in the photic pattern during the subjective night when applied in 10 pM to 1 nM doses. This appears to be mediated via a glutamatergic mechanism, possibly by potentiation of NMDA currents as is seen at 10-100 pM. Given at higher doses (>10 nM), PACAP shifts in the subjective day, apparently via activation of adenylate cyclase and increased intracellular cAMP. These results indicate dose and phase specificity of the effects of PACAP, and a new role as a transmitter in the retinohypothalamic tract.
哺乳动物体内的内源性昼夜节律起搏器位于下丘脑的视交叉上核（SCN）。各种信号可以重置昼夜节律相位，从而使内部节律与环境周期同步，这些效应可以通过体外方法测量SCN的相位偏移来进行研究。尽管垂体腺苷酸环化酶激活肽（PACAP）定位于视网膜输入到SCN的区域，但据报道它仅在主观白天改变生物钟相位（Hannibal等人，1997年），而光仅在主观夜间改变相位。在本研究中，我们表明，当以10 pM至1 nM的剂量应用时，PACAP可以在主观夜间以光照模式重置生物钟。这似乎是通过谷氨酸能机制介导的，可能是通过增强NMDA电流，就像在10 - 100 pM时看到的那样。以更高剂量（>10 nM）给予时，PACAP在主观白天发生相位偏移，显然是通过激活腺苷酸环化酶和增加细胞内cAMP。这些结果表明PACAP作用的剂量和相位特异性，以及它作为视网膜下丘脑束中一种递质的新作用。
