Neurotensin(8-13): comparison of novel analogs for stimulation of cyclic GMP formation in neuroblastoma clone N1E-115 and receptor binding to human brain and intact N1E-115 cells.
Neurotensin(8-13): comparison of novel analogs for stimulation of cyclic GMP formation in neuroblastoma clone N1E-115 and receptor binding to human brain and intact N1E-115 cells.
复制标题
神经降压素 (8-13)：比较刺激神经母细胞瘤克隆 N1E-115 中环 GMP 形成的新型类似物以及与人脑和完整 N1E-115 细胞结合的受体。
DOI：
10.1016/0006-2952(89)90637-0
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发表时间：
1989
影响因子：
5.8
通讯作者：
Richelson,E
中科院分区：
文献类型：
--
作者：
Gilbert,JA;McCormick,DJ;Pfenning,MA;Kanba,KS;Enloe,LJ;Moore,A;Richelson,E
神经紧张素（8-13）是神经紧张素的羧基末端部分，与天然神经紧张素相比，它与完整的神经母细胞瘤N1E-115细胞和人脑组织的结合能力强4-50倍，并能刺激N1E-115克隆细胞内循环GMP的产生和肌醇磷脂的水解(Gilbert JA, Richelson E,Eur J Pharmacol99: 245-246, 1984; Gilbert JAet al.,Biochem Pharmacol35: 391-397, 1986; Kanba KSet al.,J neurochem446: 946-952, 1986；和Kanba KS和Richelson E，生物化学药物36:869-874,1987)。合成了一系列新的神经紧张素类似物（8-13），并进行了结构-活性研究，比较了这些肽在完整的神经母细胞瘤克隆N1E-115中刺激细胞内环状GMP产生的能力，以及抑制[3H]神经紧张素与这些细胞和人脑膜制剂结合的能力。在克隆N1E-115的研究中，发现itsEC50、生化活性和itskd的结合能力之间存在直接相关。此外，在这些细胞上与神经紧张素受体结合的肽skd与人脑组织中与神经紧张素受体结合的肽skd之间存在很强的相关性。在这项研究中，对神经紧张素的生化和结合活性很重要的残基（8-13）被证明与天然神经紧张素功能完整性所必需的氨基酸相同（Gilbert JAet al.,Biochem Pharmacol35: 391-397, 1986）。
Neurotensin(8–13), the carboxyl-terminal portion of neurotensin, is 4–50 times more potent than native neurotensin in binding to intact neuroblastoma N1E-115 cells and human brain tissue and in stimulation of intracellular cyclic GMP production and inositol phospholipid hydrolysis in clone N1E-115 (Gilbert JA and Richelson E,Eur J Pharmacol99: 245–246, 1984; Gilbert JAet al.,Biochem Pharmacol35: 391–397, 1986; Kanba KSet al.,J Neurochem46: 946–952, 1986; and Kanba KS and Richelson E,Biochem Pharmacol36: 869–874, 1987). A series of novel analogs of neurotensin (8–13) was synthesized, and a structure-activity study was done comparing the abilities of these peptides to stimulate intracellular cyclic GMP production in intact neuroblastoma clone N1E-115 and to inhibit the binding of [3H]neurotensin to these cells and to membranal preparations from human brain. A direct correlation was found for each analog between itsEC50, for biochemical activity and itsKDfor binding ability in studies with clone N1E-115. Furthermore, a strong correlation existed for each peptide between itsKDfor binding to neurotensin receptors on these cells and itsKDfor binding to neurotensin receptors in human brain tissue. In this study, the residues that were important to the biochemical and binding activities of neurotensin (8–13) proved to be identical to the amino acids that are necessary for the functional integrity of native neurotensin (Gilbert JAet al.,Biochem Pharmacol35: 391–397, 1986).