Köves K, Arimura A, Görcs T G, Somogyvári-Vigh A
Department of Anatomy, Tulane University School of Medicine, New Orleans, La.
Neuroendocrinology. 1991 Aug;54(2):159-69. doi: 10.1159/000125864.
Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are structurally similar, share the same high affinity site in same peripheral tissues and increase the intracellular content of adenylate cyclase. To establish which neural circuits are signaling with each of these two peptides, we systematically compared the immunohistochemical distribution of PACAP and VIP in selected rat forebrain regions using previously characterized antiserum. The PACAP antiserum recognized both PACAP27 and PACAP38, and PACAP immunoreactivity was unaffected by preincubation with various other peptides. PACAP-immunoreactive perikarya and fibers were observed in both hypothalamic and extrahypothalamic regions. In the hypothalamus PACAP perikarya were located in the supraoptic, paraventricular, anterior commissural, periventricular, and perifornical nuclei. In intact rats PACAP immunolabeled fibers were present in the internal zone of the median eminence and posterior pituitary. One week after hypophysectomy the intensity of staining in the internal zone was enhanced and immunoreactive fibers appeared in the external zone of the median eminence. Two or 3 weeks later a dense fiber network was observed around the portal capillaries in the external zone, and immunoreactive material further accumulated in the fibers of the internal zone. PACAP-immunoreactive perikarya and fibers were also observed in several extrahypothalamic regions including central thalamic nuclei, amygdaloid complex, bed nucleus of stria terminalis, septum, hippocampus and cingulate, and entorhinal cortices. In the lateral septum and entorhinal cortex PACAP fibers surrounded unstained neuronal cell bodies and small blood vessels. In intact rats, VIP-immunoreactive perikarya were present in all regions of the cerebral cortex, hippocampus, amygdaloid complexus and in the suprachiasmatic nucleus, but not in the paraventricular and supraoptic nuclei. In colchicine-treated rats the VIP perikarya appeared in the preoptic area and paraventricular nucleus. The fibers were organized in two main pathways: the stria terminalis and an ascending pathway from the suprachiasmatic nucleus to the paraventricular area. Hypophysectomy induced the appearance of VIP-immunoreactive fibers in the internal zone of the median eminence and perikarya in the supraoptic and paraventricular nuclei in addition to the suprachiasmatic nucleus. The dissimilar distributions of PACAP and VIP suggest that PACAP neural circuits are independent of that of VIP in the rat forebrain. These findings support possible multifunctional roles for PACAP as a posterior pituitary hormone, a hypophysiotrophic factor, and a neurotransmitter/neuromodulator.
垂体腺苷酸环化酶激活多肽（PACAP）和血管活性肠多肽（VIP）在结构上相似，在相同的外周组织中共享相同的高亲和力位点，并增加腺苷酸环化酶的细胞内含量。为了确定这两种多肽分别通过哪些神经回路进行信号传导，我们使用先前鉴定的抗血清，系统地比较了PACAP和VIP在选定的大鼠前脑区域的免疫组织化学分布。PACAP抗血清可识别PACAP27和PACAP38，并且PACAP免疫反应性不受与其他各种多肽预孵育的影响。在丘脑下部和丘脑外区域均观察到PACAP免疫反应性的核周体和纤维。在丘脑中，PACAP核周体位于视上核、室旁核、前连合核、室周核和穹窿周核。在完整大鼠中，PACAP免疫标记纤维存在于正中隆起的内侧带和垂体后叶。垂体切除术后一周，内侧带的染色强度增强，免疫反应性纤维出现在正中隆起的外侧带。两到三周后，在外侧带的门静脉毛细血管周围观察到密集的纤维网络，免疫反应性物质在内侧带的纤维中进一步积累。在包括丘脑中央核、杏仁复合体、终纹床核、隔区、海马、扣带回和内嗅皮质在内的几个丘脑外区域也观察到PACAP免疫反应性的核周体和纤维。在外侧隔区和内嗅皮质中，PACAP纤维围绕着未染色的神经元细胞体和小血管。在完整大鼠中，VIP免疫反应性核周体存在于大脑皮质、海马、杏仁复合体的所有区域以及视交叉上核，但不存在于室旁核和视上核。在秋水仙碱处理的大鼠中，VIP核周体出现在视前区和室旁核。纤维组织成两条主要通路：终纹和一条从视交叉上核到室旁区的上行通路。垂体切除除了在视交叉上核外，还诱导了正中隆起内侧带VIP免疫反应性纤维以及视上核和室旁核中核周体的出现。PACAP和VIP的不同分布表明，在大鼠前脑中，PACAP神经回路独立于VIP神经回路。这些发现支持了PACAP作为垂体后叶激素、促垂体因子和神经递质/神经调节剂可能具有的多种功能作用。
