Vaudry D, Gonzalez B J, Basille M, Yon L, Fournier A, Vaudry H
Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), Laboratoire de Neuroendocrinologie Cellulaire et Moléculaire, Institut National de la Santé et de la Recherche Médicale U413, Mont-Saint-Aignan, France.
Pharmacol Rev. 2000 Jun;52(2):269-324.
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.
垂体腺苷酸环化酶激活多肽（PACAP）是一种由38个氨基酸组成的肽，最初是从绵羊下丘脑提取物中分离出来的，其依据是它能够刺激垂体前叶细胞中cAMP的形成。PACAP属于血管活性肠肽（VIP）-胰高血糖素-生长激素释放因子-促胰液素超家族。从原索动物到哺乳动物的进化过程中，PACAP的序列一直保持着非常良好的保守性，这表明PACAP参与了重要生物学功能的调节。PACAP广泛分布于大脑和外周器官，尤其在内分泌胰腺、性腺以及呼吸道和泌尿生殖道中。对PACAP前体的特性分析揭示了一种PACAP相关肽的存在，但其活性尚不清楚。已鉴定出两种类型的PACAP结合位点。I型结合位点对PACAP具有高亲和力，对VIP的亲和力则低得多，而II型结合位点对PACAP和VIP具有相似的亲和力。PACAP受体的分子克隆表明存在三种不同的受体亚型，即特异性结合PACAP的PAC1受体，它与多种转导系统偶联；以及两种对PACAP和VIP无差异的VPAC1和VPAC2受体，它们主要与腺苷酸环化酶偶联。PAC1受体在大脑、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受体的广泛分布引发了大量旨在确定该肽的药理作用和生物学功能的研究。本报告综述了目前关于PACAP在中枢神经系统以及包括内分泌腺、气道、心血管和免疫系统在内的各种外周器官中的多种作用的知识，以及PACAP对多种肿瘤细胞类型的不同影响。
