Diurnal regulation of the gastrin-releasing peptide receptor in the mouse circadian clock
Diurnal regulation of the gastrin-releasing peptide receptor in the mouse circadian clock
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DOI：
10.1111/j.1460-9568.2006.04633.x
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发表时间：
2006-02-01
影响因子：
3.4
通讯作者：
Silver, R
中科院分区：
文献类型：
--
作者：
Karatsoreos, IN;Romeo, RD;Silver, R
哺乳动物的昼夜节律是由下丘脑的视交叉上核（SCN）产生的。SCN神经元是异质的，可以根据它们的功能、解剖连接、形态和/或肽能特性进行分类。我们在此聚焦于胃泌素释放肽- (GRP)和GRP受体- (GRPr)表达的SCN细胞。在体内或体外药理应用GRP可改变昼夜节律的相位，grpr缺陷小鼠表现出迟钝的光相移动。考虑到GRP在体内和体外对昼夜行为和SCN神经元活动的影响，我们研究了GRPr是否可能受到昼夜和/或昼夜控制。通过原位杂交和放射自成像受体结合，我们定位了GRPr在小鼠SCN中的位置，并确定了GRP的结合随时间的变化而变化，这些动物被置于光-暗循环中，而不是在持续黑暗的条件下。后一种结果用SCN组织的Western blot证实。总之，目前的研究结果表明，GRPr的变化是光驱动的，而不是内源性组织的。GRPr活性的日变化可能是scn内信号传导的基础，对夹带和相移很重要。
In mammals, circadian rhythms are generated by the suprachiasmatic nuclei (SCN) of the hypothalamus. SCN neurons are heterogeneous and can be classified according to their function, anatomical connections, morphology and/or peptidergic identity. We focus here on gastrin-releasing peptide- (GRP) and on GRP receptor- (GRPr) expressing cells of the SCN. Pharmacological application of GRP in vivo or in vitro can shift the phase of circadian rhythms, and GRPr-deficient mice show blunted photic phase shifting. Given the in vivo and in vitro effects of GRP on circadian behavior and on SCN neuronal activity, we investigated whether the GRPr might be under circadian and/or diurnal control. Using in situ hybridization and autoradiographic receptor binding, we localized the GRPr in the mouse SCN and determined that GRP binding varies with time of day in animals housed in a light-dark cycle but not in conditions of constant darkness. The latter results were confirmed with Western blots of SCN tissue. Together, the present findings reveal that changes in GRPr are light driven and not endogenously organized. Diurnal variation in GRPr activity probably underlies intra-SCN signaling important for entrainment and phase shifting.