Reed H E, Meyer-Spasche A, Cutler D J, Coen C W, Piggins H D
School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Eur J Neurosci. 2001 Feb;13(4):839-43. doi: 10.1046/j.0953-816x.2000.01437.x.
In mammals, the principal circadian pacemaker is housed in the hypothalamic suprachiasmatic nuclei (SCN). The SCN exhibit high levels of vasoactive intestinal polypeptide (VIP) immunoreactivity and two of the three VIP receptors, VPAC(2) and PAC(1), are found in the rat SCN. However, the role of VIP in the SCN remains unclear. In this study, we examined the phase-resetting actions of VIP and selective VIP receptor agonists on the electrical activity rhythm of rat SCN neurons in vitro. Application of VIP during the subjective day did not shift the peak in the firing rate rhythm. However, VIP treatment during the early or late subjective night evoked a small phase delay or a large phase advance, respectively. The phase-advancing effect of VIP was reproduced by the novel VPAC(2) receptor agonist RO 25-1553, but not by pituitary adenylate cyclase-activating peptide (a potent PAC(1) receptor agonist), or by [K15,R16,L27]VIP(1-7)/GRF(8-27), a novel, selective VPAC(1) receptor agonist. These data show that VIP phase-dependently phase-resets the rodent SCN pacemaker in vitro, presumably via the VPAC(2) receptor. As the pattern of phase-shifting evoked by VIP and RO 25-1553 resembles the phase-resetting actions of light on rodent behavioural rhythms, these data support a role for VIP and the VPAC(2) receptor in photic entrainment of the rodent circadian pacemaker.
在哺乳动物中，主要的昼夜节律起搏器位于下丘脑视交叉上核（SCN）。SCN显示出高水平的血管活性肠肽（VIP）免疫反应性，并且在大鼠SCN中发现了三种VIP受体中的两种，即VPAC(2)和PAC(1)。然而，VIP在SCN中的作用仍不清楚。在本研究中，我们在体外研究了VIP和选择性VIP受体激动剂对大鼠SCN神经元电活动节律的相位重置作用。在主观白天应用VIP并未改变放电频率节律的峰值。然而，在主观夜晚早期或晚期给予VIP处理分别引起了小的相位延迟或大的相位提前。新型VPAC(2)受体激动剂RO 25-1553重现了VIP的相位提前效应，但垂体腺苷酸环化酶激活肽（一种有效的PAC(1)受体激动剂）或新型选择性VPAC(1)受体激动剂[K15,R16,L27]VIP(1-7)/GRF(8-27)则没有。这些数据表明，VIP在体外可通过VPAC(2)受体相位依赖性地重置啮齿动物SCN起搏器。由于VIP和RO 25-1553引起的相位移动模式类似于光对啮齿动物行为节律的相位重置作用，这些数据支持了VIP和VPAC(2)受体在啮齿动物昼夜节律起搏器的光调节中的作用。
