Deutsch P J, Schadlow V C, Barzilai N
Department of Medicine, Cornell University Medical College, New York, New York.
J Neurosci Res. 1993 Jun 15;35(3):312-20. doi: 10.1002/jnr.490350311.
Permanent cell lines from human neuroblastoma, a sympathoadrenal malignancy, are known to exhibit a more neuronal phenotype characterized by outgrowth of long processes in response to multiple second messenger analogs. In this report we demonstrate that the 38-amino acid form of a peptide homologous to vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP), as well as the 27-amino acid form of PACAP, induce NB-OK human neuroblastoma cells to extrude cellular processes within 5 hr of treatment with either peptide at 10(-8) M. Treatment of NB-OK cells with PACAP38 or PACAP27 at 10(-8) M for 1 hr also elevates cAMP content greater than 100-fold and inositol lipid turnover 11- to 12-fold. VIP acutely induces process outgrowth and elevates intracellular second messenger levels in NB-OK cells only at higher concentrations, 10(-6) M or greater. In contrast to the equipotency of PACAP27 and PACAP38 in stimulating the outgrowth of processes observed after 5 hr of treatment, PACAP38 is much more potent than PACAP27 when NB-OK cells are scored for process outgrowth after 72 hr of treatment. Correlating with the extended time course over which morphologic changes are seen with PACAP38, cAMP levels remain elevated for a more prolonged time span during treatment with PACAP38 than PACAP27. After 72 hr of treatment with PACAP38 versus treatment with PACAP27, cAMP levels are elevated 10-fold versus 3-fold, respectively. PACAP38 at 10(-8) M also induces process outgrowth in two additional human neuroblastoma lines tested, SMS-KAN and LA-N-1, whereas PACAP27 and VIP at the same concentration are less effective.(ABSTRACT TRUNCATED AT 250 WORDS)
源自人神经母细胞瘤（一种交感肾上腺恶性肿瘤）的永久细胞系，已知会表现出更具神经元特征的表型，其特点是在多种第二信使类似物的作用下长出长突起。在本报告中，我们证明与血管活性肠肽（VIP）同源的一种38个氨基酸的肽形式、垂体腺苷酸环化酶激活肽（PACAP）以及27个氨基酸的PACAP形式，在以10⁻⁸ M的任一肽处理后5小时内，可诱导NB - OK人神经母细胞瘤细胞伸出细胞突起。用10⁻⁸ M的PACAP38或PACAP27处理NB - OK细胞1小时，也会使环磷酸腺苷（cAMP）含量升高超过100倍，肌醇脂质周转率升高11至12倍。VIP仅在更高浓度（10⁻⁶ M或更高）时才会急性诱导NB - OK细胞的突起生长并提高细胞内第二信使水平。与处理5小时后观察到的PACAP27和PACAP38在刺激突起生长方面的等效性相反，当在处理72小时后对NB - OK细胞的突起生长进行评分时，PACAP38比PACAP27更有效。与用PACAP38观察到形态变化的延长时间过程相关，在用PACAP38处理期间，cAMP水平比用PACAP27处理时在更长的时间内保持升高。在用PACAP38处理72小时与用PACAP27处理相比，cAMP水平分别升高10倍和3倍。10⁻⁸ M的PACAP38在另外两种测试的人神经母细胞瘤系SMS - KAN和LA - N - 1中也诱导突起生长，而相同浓度的PACAP27和VIP效果较差。（摘要截断于250字）
