Arimura A
Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Jpn J Physiol. 1998 Oct;48(5):301-31. doi: 10.2170/jjphysiol.48.301.
PACAP is a pleiotropic neuropeptide that belongs to the secretin/glucagon/VIP family. PACAP functions as a hypothalamic hormone, neurotransmitter, neuromodulator, vasodilator, and neurotrophic factor. Its structure has been remarkably conserved during evolution. The PACAP receptor is G protein-coupled with seven transmembrane domains and also belongs to the VIP receptor family. PACAP, but not VIP, binds to PAC1-R, whereas PACAP and VIP bind to VPAC1-R and VPAC2-R with a similar affinity. Despite the sizable homology of the structures of PACAP and VIP and their receptors, the distribution of these peptides and receptors is quite different. At least eight subtypes of PACAP specific, or PAC1-R, result from alternate splicing. Each subtype is coupled with specific signaling pathways, and its expression is tissue or cell specific. Although PACAP fulfills most requirements for a physiological hypothalamic hypophysiotropic hormone, it does not consistently stimulate secretion of the adenohypophysial hormones, except for stimulation of IL-6 release from the FS cells of the pituitary. The major regulatory role of PACAP in pituitary cells appears to be the regulation of gene expression of pituitary hormones and/or regulatory proteins that control growth and differentiation of the pituitary glandular cells. These effects appear to be exhibited directly and indirectly through a paracrine or autocrine action. Although PACAP stimulates the release of AVP, the physiological role of neurohypophysial PACAP remains unknown. One important action of PACAP in the endocrine system is its role as a potent secretagogue for adrenaline from the adrenal medulla through activation of TH. PACAP also stimulates the release of insulin and increases [Ca2+]i from pancreatic beta-cells at an extremely small concentration. The stage-specific expression of PACAP in testicular germ cells during spermatogenesis suggests its regulatory role in the maturation of germ cells. In the ovary, PACAP is transiently expressed in the granulosa cells of the preovulatory follicles and appears to be involved in the LH-induced cellular events in the ovary, including prevention of follicular apoptosis. In the central nervous system, PACAP acts as a neurotransmitter or neuromodulator, which has been supported by IHC and electrophysiological methods. More important, PACAP is a neurotrophic factor that may play an important role during the development of the brain. In the adult brain, PACAP appears to function as a neuroprotective factor that attenuates the neuronal damage resulting from various insults.
垂体腺苷酸环化酶激活肽（PACAP）是一种多效性神经肽，属于促胰液素/胰高血糖素/血管活性肠肽（VIP）家族。PACAP具有下丘脑激素、神经递质、神经调质、血管舒张剂和神经营养因子等功能。其结构在进化过程中得到了显著的保守。PACAP受体是与七个跨膜结构域偶联的G蛋白偶联受体，也属于VIP受体家族。PACAP能与PAC1-R结合，而VIP则不能；PACAP和VIP能以相似的亲和力与VPAC1-R和VPAC2-R结合。尽管PACAP和VIP及其受体的结构有相当大的同源性，但这些肽和受体的分布却大不相同。PACAP特异性受体或PAC1-R至少有八种亚型是由可变剪接产生的。每种亚型都与特定的信号通路偶联，其表达具有组织或细胞特异性。尽管PACAP满足了作为生理性下丘脑促垂体激素的大多数要求，但除了刺激垂体FS细胞释放白细胞介素-6外，它并不能持续刺激腺垂体激素的分泌。PACAP在垂体细胞中的主要调节作用似乎是调节垂体激素和/或控制垂体腺细胞生长和分化的调节蛋白的基因表达。这些作用似乎是通过旁分泌或自分泌作用直接和间接表现出来的。尽管PACAP能刺激抗利尿激素（AVP）的释放，但神经垂体PACAP的生理作用仍不清楚。PACAP在内分泌系统中的一个重要作用是通过激活酪氨酸羟化酶（TH），作为肾上腺髓质肾上腺素的强效促分泌素。PACAP还能以极低的浓度刺激胰岛素的释放，并增加胰腺β细胞内的钙离子浓度（[Ca2+]i）。PACAP在精子发生过程中在睾丸生殖细胞中的阶段特异性表达表明其在生殖细胞成熟中的调节作用。在卵巢中，PACAP在排卵前卵泡的颗粒细胞中短暂表达，似乎参与了卵巢中促黄体生成素（LH）诱导的细胞事件，包括防止卵泡凋亡。在中枢神经系统中，PACAP作为神经递质或神经调质发挥作用，这已得到免疫组织化学（IHC）和电生理方法的支持。更重要的是，PACAP是一种神经营养因子，可能在大脑发育过程中发挥重要作用。在成体大脑中，PACAP似乎作为一种神经保护因子发挥作用，减轻各种损伤导致的神经元损伤。
