Ashur-Fabian O, Giladi E, Brenneman D E, Gozes I
Department of Clinical Biochemistry, Sackler School of Medicine, Tel Aviv University, Israel.
J Mol Neurosci. 1997 Dec;9(3):211-22. doi: 10.1007/BF02800503.
Vasoactive intestinal peptide (VIP) has been shown to be a potent promoter of neuronal survival. Pituitary adenylate cyclase-activating peptide (PACAP), a homologous peptide, shares activity and receptor molecules with VIP. The neuroprotective effects of VIP have been shown to be mediated via astroglial-derived molecules. Utilizing a battery of antisense oligodeoxynucleotides directed against the multiple cloned VIP-preferring (VIP receptors 1 and 2) or PACAP-preferring receptors (six splice variants derived from the same gene transcript), the authors have demonstrated the existence of a specific PACAP receptor splice variant (PACAP4 or hop2) on astrocytes as well as a VIP type2 receptor. The identification of the receptors was achieved by incubation of the cells in the presence of the specific antisense oligodeoxynucleotide followed by radiolabeled VIP binding and displacement. Polymerase chain reaction (PCR) coupled to direct sequencing identified the expression of the PACAP4-hop2 receptor splice variant in astrocytes. Neuronal survival assays were conducted in mixed neuronal-glial cultures derived from newborn rat cerebral cortex. When these cultures were exposed to the battery of the antisense oligodeoxynucleotides, in serum-free media, only the PACAP-specific ones (e.g., hop2-specific) had an effect in decreasing neuronal cell counts. Thus, the VIP neuronal survival effect is mediated, at least in part, via a specific PACAP receptor (containing a unique insertion of 27 amino acids--the hop2 cassette). These data indicate that a hop2-like PACAP/VIP receptor is the receptor that mediates neurotropism.
血管活性肠肽（VIP）已被证明是神经元存活的有力促进剂。垂体腺苷酸环化酶激活肽（PACAP），一种同源肽，与VIP共享活性和受体分子。VIP的神经保护作用已被证明是通过星形胶质细胞衍生的分子介导的。作者利用一系列针对多个克隆的VIP偏好性（VIP受体1和2）或PACAP偏好性受体（来自同一基因转录本的六个剪接变体）的反义寡脱氧核苷酸，证明了星形胶质细胞上存在一种特定的PACAP受体剪接变体（PACAP4或hop2）以及VIP 2型受体。通过在特定反义寡脱氧核苷酸存在下孵育细胞，随后进行放射性标记的VIP结合和置换来实现受体的鉴定。聚合酶链反应（PCR）结合直接测序确定了PACAP4-hop2受体剪接变体在星形胶质细胞中的表达。在源自新生大鼠大脑皮层的混合神经元-胶质细胞培养物中进行神经元存活测定。当这些培养物在无血清培养基中暴露于一系列反义寡脱氧核苷酸时，只有PACAP特异性的（例如，hop2特异性的）对减少神经元细胞数量有影响。因此，VIP的神经元存活作用至少部分是通过一种特定的PACAP受体（包含27个氨基酸的独特插入——hop2盒）介导的。这些数据表明，一种类似hop2的PACAP/VIP受体是介导神经趋向性的受体。
