Zhou Cheng-Ji, Shioda Seiji, Yada Toshihiko, Inagaki Nobuya, Pleasure Samuel J, Kikuyama Sakae
Department of Neurology, University of California, San Francisco, CA 94143-0435, USA.
Curr Protein Pept Sci. 2002 Aug;3(4):423-39. doi: 10.2174/1389203023380576.
Pituitary adenylate cyclase-activating polypeptide (PACAP) was originally isolated from the ovine brain in 1989 as a novel hypothalamic hormone that potently activates adenylate cyclase to produce cyclic AMP in pituitary cells. This neuropeptide belongs to the secretin/glucagon/vasoactive intestinal peptide (VIP) superfamily, and exists in two amidated forms as PACAP38 (38-amino acid residues) and PACAP27 derived from the same precursor. The primary structure of PACAP has been remarkably conserved throughout evolution among tunicata, ichthyopsida, amphibia and mammalia, and a PACAP-like neuropeptide has also been determined in Drosophila. Both PACAP and its receptors are mainly distributed in the nervous and endocrine systems showing pleiotropic functions with high potency. There are three types of receptors with high PACAP-binding affinity and with different tissue-distribution patterns. All of them belong to G-protein-coupled receptor superfamily with seven transmembrane domains. PAC(1) is the PACAP-specific receptor and exists in at least eight splice variants which couple to different intracellular signal transduction pathways. VPAC(1) and VPAC(2) are the common receptors for both PACAP and VIP, which are coupled to adenylate cyclase. This review article presents and discusses an update on PACAP research and its pleiotropic physiological functions based on multiple receptor-mediated signaling mechanisms in both the central and peripheral nervous system, including the regulation of hypothalamic neurosecretion, homeostatic control of circadian clock and behavioral actions, involvement in learning and memory processes, neuroprotective effects such as anti-apoptosis and response to injury and inflammation, and neural ontogenetic functions on proliferation/differentiation processes from early stages.
垂体腺苷酸环化酶激活多肽（PACAP）最初于1989年从绵羊脑中分离出来，是一种新型下丘脑激素，能有效激活腺苷酸环化酶，在垂体细胞中产生环磷酸腺苷。这种神经肽属于促胰液素/胰高血糖素/血管活性肠肽（VIP）超家族，以两种酰胺化形式存在，即PACAP38（38个氨基酸残基）和源自同一前体的PACAP27。在被囊动物、鱼类、两栖动物和哺乳动物的整个进化过程中，PACAP的一级结构一直保持着显著的保守性，在果蝇中也确定了一种类似PACAP的神经肽。PACAP及其受体主要分布在神经和内分泌系统中，具有高效的多效性功能。有三种对PACAP具有高结合亲和力且组织分布模式不同的受体。它们都属于具有七个跨膜结构域的G蛋白偶联受体超家族。PAC(1)是PACAP特异性受体，至少存在八种剪接变体，它们与不同的细胞内信号转导途径偶联。VPAC(1)和VPAC(2)是PACAP和VIP的共同受体，与腺苷酸环化酶偶联。本文综述并讨论了基于中枢和外周神经系统中多种受体介导的信号机制的PACAP研究及其多效生理功能的最新进展，包括下丘脑神经分泌的调节、生物钟的稳态控制和行为作用、参与学习和记忆过程、抗凋亡等神经保护作用以及对损伤和炎症的反应，以及在早期增殖/分化过程中的神经发生功能。
