Neurotensin(8-13) is the core active fragment of neurotensin and functions as a biologically active neurotensin receptor (NTSR1) agonist. By binding to NTSR1 with high affinity (Kd≈1–10nM), Neurotensin(8-13) activates the Gq/11 protein signaling pathway, thereby regulating intracellular calcium ion concentration and the activity of protein kinase C (PKC)[1-2]. Neurotensin(8-13) can be used in research related to pain management, psychiatric disorders (such as schizophrenia and depression), and tumor-targeted therapy[3-4].
In vitro, human colon adenocarcinoma HT-29 cells were treated with Neurotensin(8-13) (3–100nM) for 1–2 hours. Neurotensin(8-13) significantly induced rapid internalization mediated by the neurotensin receptor NTR1 and caused a time-dependent downregulation of NTR1 receptors on the cell surface[5]. Human non-small cell lung cancer cells NCI-H1299 were treated with Neurotensin(8-13) (100nM) for 2.5 minutes, which significantly induced tyrosine phosphorylation of focal adhesion kinase (FAK). After treating NCI-H1299 cells with Neurotensin(8-13) (10nM) for 24 hours, Neurotensin(8-13) promoted the proliferation of NCI-H1299 cells[6].
In vivo, normotensive rats were injected via the femoral vein with Neurotensin(8-13) (0.1–100nmol/kg). Neurotensin(8-13) dose-dependently reduced diastolic and systolic blood pressure without altering heart rate and showed no direct vasodilatory effect on isolated rat aortic rings[7]. Male Long-Evans rats received microinjections of Neurotensin(8-13) (3nmol in 0.5μl) into the ventral midbrain tegmental area. Neurotensin(8-13) significantly enhanced the reward effect of brain stimulation in the midbrain central gray matter 15–55 minutes after injection[8].
References:
[1] Gilbert JA, McCormick DJ, Pfenning MA, et al. 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. Biochem Pharmacol. 1989 Oct 1;38(19):3377-82.
[2] Cocioabă D, Fonseca AI, Leonte R, et al. Neurotensin (8-13) and Neuromedin N Neuropeptides Radiolabelling with Copper-64 Produced on Solid or Liquid Targets. Molecules. 2024 Mar 20;29(6):1390.
[3] Li XM, Von Euler G, Hedlund PB, et al. The C-terminal neurotensin-(8-13) fragment potently modulates rat neostriatal dopamine D2 receptors. Eur J Pharmacol. 1993 Mar 30;234(1):125-8.
[4] Pinnock RD, Woodruff GN. The non-peptide neurotensin receptor antagonist SR48692 is not a potent antagonist of neurotensin(8-13) responses of rat substantia nigra neurones in vitro. Neurosci Lett. 1994 May 19;172(1-2):175-8.
[5] García-Garayoa E, Bläuenstein P, Bruehlmeier M, et al. Preclinical evaluation of a new, stabilized neurotensin(8--13) pseudopeptide radiolabeled with (99m)tc. J Nucl Med. 2002 Mar;43(3):374-83.
[6] Leyton J, Garcia-Marin L, Jensen RT, et al. Neurotensin causes tyrosine phosphorylation of focal adhesion kinase in lung cancer cells. Eur J Pharmacol. 2002 May 10;442(3):179-86.
[7] Di Paola ED, Richelson E. Cardiovascular effects of neurotensin and some analogues on rats. Eur J Pharmacol. 1990 Jan 17;175(3):279-83.
[8] Rompré PP, Gratton A. Mesencephalic microinjections of neurotensin-(1-13) and its C-terminal fragment, neurotensin-(8-13), potentiate brain stimulation reward. Brain Res. 1993 Jul 9;616(1-2):154-62.
Neurotensin(8-13)是神经降压素（Neurotensin）的核心活性片段，Neurotensin(8-13)是具有生物活性的神经降压素受体（NTSR1）激动剂，通过与NTSR1高亲和力结合（Kd≈1-10nM）激活Gq/11蛋白信号通路，进而调控细胞内钙离子浓度及蛋白激酶C（PKC）的活性[1-2]。Neurotensin(8-13)可用于疼痛管理、精神疾病（如精神分裂症、抑郁症）及肿瘤靶向治疗的相关研究[3-4]。
在体外，Neurotensin(8-13)（3-100nM）处理人结肠腺癌HT-29细胞1-2小时，Neurotensin(8-13)显著诱导神经降压素受体NTR1介导的快速内化，并引起细胞表面NTR1受体的时间依赖性下调[5]。Neurotensin(8-13)（100nM）处理人非小细胞肺癌细胞NCI-H1299 2.5分钟，可显著诱导黏着斑激酶（FAK）的酪氨酸磷酸化。Neurotensin(8-13)（10nM）处理NCI-H1299细胞24小时能促进NCI-H1299细胞增殖[6]。
在体内，Neurotensin(8-13)经股静脉注射处理正常血压大鼠（0.1-100nmol/kg），Neurotensin(8-13)以剂量依赖方式降低舒张压和收缩压，但不改变心率，且对离体大鼠主动脉环无直接血管舒张作用 [7]。Neurotensin(8-13)经中脑腹内侧被盖区微注射（3nmol; 5μl）处理雄性Long-Evans大鼠，Neurotensin(8-13)在注射后15-55分钟显著增强中脑中央灰质脑刺激奖励效应[8]。