Modulation of central sodium / osmo-homeostatic mechanisms by novel peptides-Integrative studies

通过内皮素系统对高碱性盐水（HS）加载的适应性反应的修改：大分子和半分子分化的超分子核的超分子核（PVN）。PVN分部是在HS加载后激活的，并通过预处理与vasopressin （AVP） V1受体拮抗剂（OPC-21268）的影响来模拟使用类似Fos免疫活性（FLI）的表达。两个PVN分支都被激活了，是一个整体的分支，而不是一个大尺度的分支，是通过治疗来增强的，并表明了AVP系统对sympathetic启动子神经元的抑制作用。在添加中，对心血管系统的反应和FLI表达在有意识的气相饱和-过度表达的转基因（Tg）老鼠被测试。中央HS加载增强的动脉血液压力（ABP）和FLI表达在PVN、超光学核（SON）、中光学核（MnPO）中 ... More e area postrema （AP）， and the organum vasculosum laminae terminalis （OVLT） in Tg rats比较to the control rats。用OPC-21268阻断了ABP中的增加，并明显地减少了由HS加载在Tg大鼠中的PVN的大尺度分区中的FLI表达。新的肽在人体水平衡和心血管系统的调节中的作用：皮质激素释放因子（CRF）和神经激素U （NMU）对大鼠PVN neurons were studed using whole-cell patch-clamp recordings。在当前钳位、通用报告格式和NMU增加了神经元基础发射率和依赖性神经元在剂量-依赖性术语中。在电压钳下，两种肽都明显地增加了超极化激活的疗法电流（IH）在剂量-依赖性的指示器中。研究结果显示，通过CRF受体1和NMU受体2调节PVN超声波神经功能的亚群，通过HCN离子通道活动的潜力，通过CRF受体1和NMU受体2调节CRF和NMU的结果。在增材中，内旋（一. C. V）另一种新型肽、神经肽W （NPW）、increased ABP、heart rate、plasma norepinephrine和epinephrine concentrations in conscious rats。Furthermore，i. c. v. NPW兴奋的22个，抑制的7个，但没有影响6个35个PVN神经元在有意识的、自由移动的老鼠中测试。vasopressin V1 b受体knockout （V1 b-/-）的功能分析：每日饮酒行为和renal secretory函数在V1 b-/-和控制（V1 b +/+） mice。在添加剂、身体温度和动力仪活动中，用生物测量系统进行了测量。Baseline Daily water intake and urine volume were larger in V1b-/- mice than in V1b+/+ mice. V1 b-/-老鼠比V1 b +/+老鼠的身体温度和氧消耗在V1 b-/-比V1 b +/+老鼠更重要。下一步，老鼠被要求在48小时内被水消耗，在这种条件下，它的身体温度在时间上下降，而且对V1 b-/-比V1 b +/+老鼠的下降明显要大。V1 b受体可能是，至少在零件中，并在身体水平衡和身体温度调节中加入。Less（低）

・Modification of adaptive responses to hypertonic saline (HS) loading by the endogenous vasopressin system: The paraventricular nucleus (PVN) of the hypothalamus consists of the magnocellular and parvicellular divisions. The PVN division that is activated following HS loading and is affected by pretreatment with vasopressin (AVP) V1 receptor antagonist (OPC-21268) was examined using the expression of Fos-like immunoreactivity (FLI). Although both PVN divisions were activated, the parvocellular division, but not the magnocellular division, was enhanced by the pretreatment, indicating the inhibitory action of the AVP system on the sympathetic promotor neurons in the PVN. In addition, the responses of the cardiovascular system and FLI expression to HS loading in conscious vasopressin-overexpressing transgenic (Tg) rats were examined. Central HS loading enhanced arterial blood pressure (ABP) and FLI expression in the PVN, the supraoptic nucleus (SON), the median preoptic nucleus (MnPO), th … More e area postrema (AP), and the organum vasculosum laminae terminalis (OVLT) in Tg rats compared to the control rats. The pretreatment with OPC-21268 blocked the increase in ABP and significantly decreased the FLI expression in the magnocellular division of the PVN induced by HS loading in the Tg rats.・Roles of novel peptides in the regulation of body water balance and the cardiovascular system: The effects of corticotrophin-releasing factor (CRF)and neuromedin U (NMU) on rat PVN neurons were studied using whole-cell patch-clamp recordings. Under current clamp, CRF and NMU increased the neuronal basal firing rate and depolarized neurons in a dose-dependent manner. Under voltage clamp, both peptides significantly increased the hyperpolarization-activated cation current (IH) in a dose-dependent manner. The results showed that CRF and NMU modulate the subpopulation of PVN parovocellular neuronal function by CRF receptor 1 and NMU receptor 2, respectively, via the potentiation of HCN ion channel activity. In addition, intracerebroventricular (i.c.v.)administration of another novel peptide, neuropeptide W (NPW), increased ABP, heart rate, and plasma norepinephrine and epinephrine concentrations in conscious rats. Furthermore, i.c.v. administration of NPW excited 22 and inhibited 7 but did not affect 6 out of 35 PVN neurons tested in conscious, freely moving rats.・Functional analysis of vasopressin V1b receptor knockout (V1b-/-)mice: Daily drinking behavior and renal secretory function were measured in V1b-/- and control (V1b+/+) mice. In addition, body temperature and locomotor activity were measured with a biotelemetry system. The baseline daily water intake and urine volume were larger in V1b-/- mice than in V1b+/+ mice. V1b-/- mice had significantly higher locomotor activity than did wild-type mice, whereas the body temperature and oxygen consumption were lower in V1b-/- than in V1b+/+ mice. Next, the mice were subjected to water deprivation for 48 hr. Under this condition, their body temperature decreased with the time course, and the decrease was significantly greater for V1b-/- than for V1b+/+ mice. The V1b receptor may be, at least in part, involved in body water balance and body temperature regulation. Less