Vasoactive intestinal polypeptide (VIP) phase-shifts the rat suprachiasmatic nucleus clock in vitro

Vasoactive intestinal polypeptide (VIP) phase-shifts the rat suprachiasmatic nucleus clock in vitro
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DOI:
10.1046/j.0953-816x.2000.01437.x
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发表时间:
2001-02-01
影响因子:
3.4
通讯作者:
Piggins, HD
Piggins, HD
中科院分区:
医学3区
文献类型:
--
作者:
Reed, HE;Meyer-Spasche, A;Piggins, HD

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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显示高水平的血管活性肠多肽(VIP)免疫反应性,并且在大鼠SCN中发现三种VIP受体中的两种,VPAC(2)和PAC(1)。然而,VIP在SCN中的作用仍不清楚。在这项研究中,我们研究了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。在主观日期间应用VIP并没有改变放电率节律的峰值。然而,VIP治疗在早期或后期主观的夜晚引起一个小的相位延迟或大的相位提前,分别。VIP的相位推进作用可由新型VPAC(2)受体激动剂RO 25-1553重现,但不能由垂体腺苷酸环化酶激活肽(一种有效的PAC(1)受体激动剂)或[K15,R16,L27]VIP(1-7)/GRF(8-27)(一种新型的选择性VPAC(1)受体激动剂)重现。这些数据表明,VIP在体外可能通过VPAC(2)受体对啮齿动物SCN起搏器进行相位依赖性相位重置。由于VIP和RO 25-1553诱发的相移模式类似于光对啮齿动物行为节律的相位重置作用,因此这些数据支持VIP和VPAC(2)受体在啮齿动物昼夜节律起搏器的光夹带中的作用。
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.