PACAP modulates rat sympathetic neuron depolarization through IP3.
PACAP modulates rat sympathetic neuron depolarization through IP3.
复制标题
PACAP 通过 IP3 调节大鼠交感神经元去极化。
DOI：
10.1111/j.1749-6632.2000.tb06965.x
复制
发表时间：
2000
影响因子：
5.2
通讯作者：
Braas,KM
中科院分区：
文献类型：
--
作者：
May,V;Beaudet,MM;Parsons,RL;Braas,KM
在过去的几年中，我们的实验室在许多人中，已经证明了生理相关的PACAP和PACAP选择性PAC 1受体作为交感神经自主生理学中的非胆碱能神经调节系统。我们已经表明，PACAP和PAC 1受体分布在适当的组织中参与交感神经功能，PACAP肽在生理相关浓度下引起交感神经元的反应，并且鉴于VIP/PACAP肽家族的良好神经营养功能，PACAP和PAC 1受体在损伤后交感神经元的发育和再生中具有潜在的作用。初步研究表明，PACAP 27和PACAP 38对颈上级神经节（SCG）交感神经元神经递质和神经肽Y（NPY）的产生和分泌具有强效作用。1，2随后，我们采用分子、细胞和生物化学方法证明了PACAP mRNA在脊髓交感节前投射神经元中向SCG的表达，3以鉴定一种特定PAC 1（短）HOP 1受体变体在大多数SCG节后神经元中的优先表达，并使用特定第二信使途径的选择性抑制剂建立，SCG受体变体有效激活多个细胞内信号级联能力。1，4-6这些结果与许多其他实验室的出色工作一致，表明颈交感干横断时SCG中PACAP免疫反应性纤维的高密度减少，7-9通过原位杂交，SCG PAC 1受体mRNA优先在节后神经元中表达，4，10，PACAP肽可能在交感神经母细胞发育中具有增殖作用。6，11神经元损伤后PACAP的表达显著增加，部分原因是转录后机制的改变，表明PACAP肽可能是再生反应的重要介质。12-14与PAC 1受体偶联的多种不同的细胞内信号传导途径、对PACAP的神经元反应的多样性和PACAP肽表达的独特调节机制都表明PACAP肽能解剖学和神经生物学系，佛蒙特大学医学院，给定健康科学大楼C421，伯灵顿，佛蒙特州05405。语音：802-656-0398;传真：802-656-8704。vmay@ zoo. UVM。edu
During the last several years, our laboratories among many others, have demonstrated the physiological relevance of PACAP and the PACAP-selective PAC1 receptor as the noncholinergic neuromodulatory system in sympathetic autonomic physiology. We have shown that PACAP and the PAC1 receptors are distributed in the appropriate tissues to participate in sympathetic function, that PACAP peptides elicit sympathetic neuronal responses at physiologically relevant concentrations, and given the well established neurotrophic functions of the VIP/PACAP family of peptides, that PACAP and PAC1 receptors have potential roles in sympathetic neuronal development and regeneration following injury. The initial studies demonstrated the potent effects of PACAP27 and PACAP38 on superior cervical ganglion (SCG) sympathetic neuron neurotransmitter and neuropeptide Y (NPY) production and secretion. 1, 2 Subsequently, we have employed molecular, cellular, and biochemical approaches to demonstrate the expression of PACAP mRNA in spinal cord sympathetic preganglionic projection neurons to the SCG, 3 to identify the preferential expression of one specific PAC1 (short) HOP1 receptor variant in the majority of SCG postganglionic neurons, and to establish, using selective inhibitors to particular second messenger pathways, the ability of that SCG receptor variant to activate potently multiple intracellular signaling cascades. 1, 4–6 These results were in agreement with the elegant work of a number of other laboratories, demonstrating that the high density of PACAP-immunoreactive fibers in the SCG is diminished on transection of the cervical sympathetic trunk, 7–9 the SCG PAC1 receptor mRNA is preferentially expressed in postganglionic neurons by in situ hybridization, 4, 10 and that PACAP peptides may have proliferative roles in sympathetic neuroblast development. 6, 11 The expression of PACAP is augmented considerably following neuronal injury, due in part to alterations in posttranscriptional mechanisms suggesting that PACAP peptides may be important mediators of the regeneration response. 12–14 The multitude of different intracellular signaling pathways coupled to the PAC1 receptor, the diversity of neuronal responses to PACAP and the unique regulatory mechanisms underlying the expression of PACAP peptides all suggest that the PACAP peptidergic aAddress for correspondence: Victor May, Ph. D., Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Given Health Science Building C421, Burlington, Vermont 05405. Voice: 802-656-0398; fax: 802-656-8704. vmay@ zoo. uvm. edu