Gilbert J A, McCormick D J, Pfenning M A, Kanba K S, Enloe L J, Moore A, Richelson E
Department of Psychiatry and Pharmacology, Mayo Clinic, Rochester, MN 55905.
Biochem Pharmacol. 1989 Oct 1;38(19):3377-82. doi: 10.1016/0006-2952(89)90637-0.
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 Pharmacol 99: 245-246, 1984; Gilbert JA et al., Biochem Pharmacol 35: 391-397, 1986; Kanba KS et al., J Neurochem 46: 946-952, 1986; and Kanba KS and Richelson E, Biochem Pharmacol 36: 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 its EC50 for biochemical activity and its KD for binding ability in studies with clone N1E-115. Furthermore, a strong correlation existed for each peptide between its KD for binding to neurotensin receptors on these cells and its KD for 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 JA et al., Biochem Pharmacol 35: 391-397, 1986.
神经降压素（8 - 13）是神经降压素的羧基末端部分，在与完整的神经母细胞瘤N1E - 115细胞和人脑组织结合、刺激克隆N1E - 115细胞内的环磷酸鸟苷生成以及肌醇磷脂水解方面，其效力比天然神经降压素强4至50倍（吉尔伯特·J·A和里切尔森·E，《欧洲药理学杂志》99：245 - 246，1984；吉尔伯特·J·A等人，《生物化学药理学》35：391 - 397，1986；神波·K·S等人，《神经化学杂志》46：946 - 952，1986；以及神波·K·S和里切尔森·E，《生物化学药理学》36：869 - 874，1987）。合成了一系列神经降压素（8 - 13）的新型类似物，并进行了结构 - 活性研究，比较这些肽在完整的神经母细胞瘤克隆N1E - 115中刺激细胞内环磷酸鸟苷生成以及抑制[³H]神经降压素与这些细胞和人脑膜制剂结合的能力。在对克隆N1E - 115的研究中，发现每种类似物的生化活性EC50与其结合能力的KD之间存在直接相关性。此外，每种肽在与这些细胞上的神经降压素受体结合的KD与其与人脑组织中神经降压素受体结合的KD之间存在很强的相关性。在本研究中，对神经降压素（8 - 13）的生化和结合活性重要的残基被证明与天然神经降压素功能完整性所需的氨基酸相同（吉尔伯特·J·A等人，《生物化学药理学》35：391 - 397，1986）。
