Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions.
Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions.
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发表时间：
2000-06
影响因子：
21.1
通讯作者：
D. Vaudry;B. Gonzalez;M. Basille;L. Yon;A. Fournier;H. Vaudry
中科院分区：
文献类型：
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作者：
D. Vaudry;B. Gonzalez;M. Basille;L. Yon;A. Fournier;H. Vaudry
垂体腺苷酸环化酶激活多肽（PACAP）是一种由38个氨基酸组成的多肽，基于其刺激垂体前叶细胞中cAMP形成的能力，首次从绵羊下丘脑提取物中分离。PACAP属于血管活性肠多肽（VIP）-胰高血糖素-生长激素释放因子-促胰液素超家族。PACAP序列在原脊索动物到哺乳动物的进化过程中保持了很好的保守性，表明PACAP参与了重要的生物学功能的调节。PACAP广泛分布于脑和外周器官，特别是内分泌胰腺、性腺、呼吸道和泌尿生殖道。PACAP前体的表征揭示了PACAP相关肽的存在，其活性仍然未知。两种类型的PACAP结合位点的特点。I型结合位点表现出对PACAP的高亲和力和对VIP的低得多的亲和力，而II型结合位点对PACAP和VIP具有相似的亲和力。PACAP受体的分子克隆显示存在三种不同的受体亚型，PACAP特异性PAC 1受体，其与几种转导系统偶联，以及两种PACAP/VIP无关性VPAC 1和VPAC 2受体，其主要与腺苷酸环化酶偶联。PAC 1受体在脑、垂体和肾上腺中特别丰富，而VPAC受体主要在肺、肝和睾丸中表达。PACAP和PACAP受体的广泛分布导致了旨在确定肽的药理学作用和生物学功能的研究爆炸。本文综述了PACAP在中枢神经系统和各种外周器官（包括内分泌腺、气道、心血管和免疫系统）中的多种作用，以及PACAP对多种肿瘤细胞类型的不同作用。
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide that was first isolated from ovine hypothalamic extracts on the basis of its ability to stimulate cAMP formation in anterior pituitary cells. PACAP belongs to the vasoactive intestinal polypeptide (VIP)-glucagon-growth hormone releasing factor-secretin superfamily. The sequence of PACAP has been remarkably well conserved during the evolution from protochordate to mammals, suggesting that PACAP is involved in the regulation of important biological functions. PACAP is widely distributed in the brain and peripheral organs, notably in the endocrine pancreas, gonads, and respiratory and urogenital tracts. Characterization of the PACAP precursor has revealed the existence of a PACAP-related peptide whose activity remains unknown. Two types of PACAP binding sites have been characterized. Type I binding sites exhibit a high affinity for PACAP and a much lower affinity for VIP whereas type II binding sites have similar affinity for PACAP and VIP. Molecular cloning of PACAP receptors has shown the existence of three distinct receptor subtypes, the PACAP-specific PAC1 receptor, which is coupled to several transduction systems, and the two PACAP/VIP-indifferent VPAC1 and VPAC2 receptors, which are primarily coupled to adenylyl cyclase. PAC1 receptors are particularly abundant in the brain and pituitary and adrenal glands whereas VPAC receptors are expressed mainly in the lung, liver, and testis. The wide distribution of PACAP and PACAP receptors has led to an explosion of studies aimed at determining the pharmacological effects and biological functions of the peptide. This report reviews the current knowledge concerning the multiple actions of PACAP in the central nervous system and in various peripheral organs including the endocrine glands, the airways, and the cardiovascular and immune systems, as well as the different effects of PACAP on a number of tumor cell types.