Waschek J A, Lelievre V, Bravo D T, Nguyen T, Muller J M
Department of Psychiatry, University of California at Los Angeles 90024, USA.
Peptides. 1997;18(6):835-41. doi: 10.1016/s0196-9781(97)00015-6.
Neuroendocrine tumors, neuroblastoma in particular, commonly express the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) and their receptors. Retinoic acid (RA) has been shown to induce differentiation of neuroblastoma cell lines, possibly by augmenting or interfering with neuropeptide autocrine loops. We sought to determine which receptor gene subtypes are expressed in selected human neuroblastoma cell lines (SH-SY5Y, IMR-32, and LA-N-5), and the effect of RA on the VIP/PACAP ligand/receptor system. Expression of both PACAP1 and VIP1/PACAP2 receptor genes was detected by Northern analysis, which characteristically encode Type I (PACAP-preferring), and Type II (bivalent VIP/PACAP) receptors, respectively. Binding experiments carried out on IMR-32 cells, using 125I VIP and 125I PACAP-27 as tracers, corroborated that both receptor subtypes were expressed. In contrast to RA upregulation of VIP binding (confirmed here in IMR-32 cells), levels of both receptor mRNAs were reduced after RA treatment. VIP mRNA in each cell line was increased by RA, whereas PACAP mRNA, detected in IMR-32 cells only, was reduced. The studies indicate that several components of the VIP/PACAP autocrine system are regulated in neuroblastoma cell lines during RA differentiation.
神经内分泌肿瘤，尤其是神经母细胞瘤，通常表达神经肽血管活性肠肽（VIP）和垂体腺苷酸环化酶激活肽（PACAP）及其受体。视黄酸（RA）已被证明可诱导神经母细胞瘤细胞系分化，可能是通过增强或干扰神经肽自分泌环来实现的。我们试图确定在选定的人类神经母细胞瘤细胞系（SH-SY5Y、IMR-32和LA-N-5）中表达哪些受体基因亚型，以及RA对VIP/PACAP配体/受体系统的影响。通过Northern分析检测到PACAP1和VIP1/PACAP2受体基因的表达，它们分别典型地编码I型（优先结合PACAP）和II型（双价VIP/PACAP）受体。使用125I VIP和125I PACAP-27作为示踪剂在IMR-32细胞上进行的结合实验证实了两种受体亚型均有表达。与RA上调VIP结合（在IMR-32细胞中得到证实）相反，RA处理后两种受体mRNA的水平均降低。RA使每个细胞系中的VIP mRNA增加，而仅在IMR-32细胞中检测到的PACAP mRNA则减少。这些研究表明，在RA诱导分化过程中，神经母细胞瘤细胞系中VIP/PACAP自分泌系统的几个组成部分受到调控。
