高亲和力神经肽Y受体拮抗剂
High-affinity neuropeptide Y receptor antagonists.
作者信息
Daniels A J, Matthews J E, Slepetis R J, Jansen M, Viveros O H, Tadepalli A, Harrington W, Heyer D, Landavazo A, Leban J J, Spaltenstein A
机构信息
Division of Pharmacology, Burroughs Wellcome Co., Research Triangle Park, NC 27709, USA.
出版信息
Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9067-71. doi: 10.1073/pnas.92.20.9067.
Abstract
Neuropeptide Y (NPY) is one of the most abundant peptide transmitters in the mammalian brain. In the periphery it is costored and coreleased with norepinephrine from sympathetic nerve terminals. However, the physiological functions of this peptide remain unclear because of the absence of specific high-affinity receptor antagonists. Three potent NPY receptor antagonists were synthesized and tested for their biological activity in in vitro, ex vivo, and in vivo functional assays. We describe here the effects of these antagonists inhibiting specific radiolabeled NPY binding at Y1 and Y2 receptors and antagonizing the effects of NPY in human erythroleukemia cell intracellular calcium mobilization perfusion pressure in the isolated rat kidney, and mean arterial blood pressure in anesthetized rats.
摘要
神经肽Y（NPY）是哺乳动物大脑中含量最为丰富的肽类递质之一。在周围组织中，它与去甲肾上腺素共同储存于交感神经末梢并共同释放。然而，由于缺乏特异性高亲和力受体拮抗剂，该肽的生理功能仍不清楚。合成了三种有效的NPY受体拮抗剂，并在体外、离体和体内功能试验中测试了它们的生物活性。我们在此描述了这些拮抗剂在抑制Y1和Y2受体上特异性放射性标记NPY结合，以及拮抗NPY对人红白血病细胞内钙动员、离体大鼠肾脏灌注压和麻醉大鼠平均动脉血压影响方面的作用。
相似文献
1
High-affinity neuropeptide Y receptor antagonists.高亲和力神经肽Y受体拮抗剂
Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9067-71. doi: 10.1073/pnas.92.20.9067.
2
Subtype selectivity and antagonistic profile of the nonpeptide Y1 receptor antagonist BIBP 3226.非肽类Y1受体拮抗剂BIBP 3226的亚型选择性及拮抗特征
J Pharmacol Exp Ther. 1995 Oct;275(1):143-9.
3
Y1 and Y2 receptor selective neuropeptide Y analogues: evidence for a Y1 receptor subclass.Y1和Y2受体选择性神经肽Y类似物：Y1受体亚类的证据
J Med Chem. 1995 Oct 27;38(22):4579-86. doi: 10.1021/jm00022a024.
4
5
Antagonistic properties of centrally truncated analogs of [D-Trp(32)]NPY.
J Med Chem. 1996 Mar 1;39(5):1142-7. doi: 10.1021/jm9505371.
6
Pharmacological evaluation of 1229U91, a novel high-affinity and selective neuropeptide Y-Y1 receptor antagonist.新型高亲和力和选择性神经肽Y-Y1受体拮抗剂1229U91的药理学评价
J Pharmacol Exp Ther. 1995 Dec;275(3):1261-6.
7
Expression cloning of a human brain neuropeptide Y Y2 receptor.一种人脑神经肽Y Y2受体的表达克隆
Mol Pharmacol. 1996 Feb;49(2):224-8.
8
Neuropeptide Y1 subtype pharmacology of a recombinantly expressed neuropeptide receptor.重组表达的神经肽受体的神经肽Y1亚型药理学
Mol Pharmacol. 1992 May;41(5):817-21.
9
10
Synthesis, structure, and antagonistic properties of des-Asn29[D-Trp28,32]NPY(27-36).去天冬酰胺29[D-色氨酸28,32]神经肽Y（27-36）的合成、结构及拮抗特性
Peptides. 1996;17(7):1113-8. doi: 10.1016/s0196-9781(96)00182-9.
引用本文的文献
1
PET Imaging of the Neuropeptide Y System: A Systematic Review.正电子发射断层扫描成像的神经肽 Y 系统：系统评价。
Molecules. 2022 Jun 9;27(12):3726. doi: 10.3390/molecules27123726.
2
In Search of NPY YR Antagonists: Incorporation of Carbamoylated Arginine, Aza-Amino Acids, or d-Amino Acids into Oligopeptides Derived from the C-Termini of the Endogenous Agonists.寻找神经肽Y Y受体拮抗剂：将氨甲酰化精氨酸、氮杂氨基酸或D-氨基酸引入源自内源性激动剂C末端的寡肽中。
ACS Omega. 2017 Jul 31;2(7):3616-3631. doi: 10.1021/acsomega.7b00451. Epub 2017 Jul 14.
3
In Vitro Mouse and Human Serum Stability of a Heterobivalent Dual-Target Probe That Has Strong Affinity to Gastrin-Releasing Peptide and Neuropeptide Y1 Receptors on Tumor Cells.对肿瘤细胞上胃泌素释放肽和神经肽Y1受体具有强亲和力的异二价双靶点探针的体外小鼠和人血清稳定性
Cancer Biother Radiopharm. 2017 Feb;32(1):24-32. doi: 10.1089/cbr.2016.2136.
4
Novel dimeric DOTA-coupled peptidic Y1-receptor antagonists for targeting of neuropeptide Y receptor-expressing cancers.新型二聚体 DOTA 偶联肽 Y1 受体拮抗剂，用于靶向表达神经肽 Y 受体的癌症。
EJNMMI Res. 2011 Sep 2;1(1):21. doi: 10.1186/2191-219X-1-21.
5
Neuropeptide Y: a physiological orexigen modulated by the feedback action of ghrelin and leptin.神经肽Y：一种受胃饥饿素和瘦素反馈作用调节的生理性食欲素。
Endocrine. 2003 Oct;22(1):49-56. doi: 10.1385/ENDO:22:1:49.
6
Development and characterization of a highly selective neuropeptide Y Y5 receptor agonist radioligand: [125I][hPP1-17, Ala31, Aib32]NPY.一种高选择性神经肽Y Y5受体激动剂放射性配体的研发与表征：[125I][hPP1-17, Ala31, Aib32]神经肽Y
Br J Pharmacol. 2003 Aug;139(7):1360-8. doi: 10.1038/sj.bjp.0705376.
7
Constitutive neuropeptide Y Y(4) receptor expression in human colonic adenocarcinoma cell lines.人结肠腺癌细胞系中组成型神经肽Y Y(4)受体的表达
Br J Pharmacol. 2001 Jan;132(1):345-53. doi: 10.1038/sj.bjp.0703815.
8
Neuropeptide Y: A hypothalamic brake restraining the onset of puberty in primates.神经肽Y：一种抑制灵长类动物青春期启动的下丘脑制动因素。
Proc Natl Acad Sci U S A. 2000 May 23;97(11):6179-84. doi: 10.1073/pnas.090099697.
9
BIIE0246, a potent and highly selective non-peptide neuropeptide Y Y(2) receptor antagonist.BIIE0246，一种强效且高度选择性的非肽类神经肽Y Y(2)受体拮抗剂。
Br J Pharmacol. 2000 Mar;129(6):1075-88. doi: 10.1038/sj.bjp.0703162.
10
[(125)I]-GR231118: a high affinity radioligand to investigate neuropeptide Y Y(1) and Y(4) receptors.[125I] -GR231118：一种用于研究神经肽Y Y(1)和Y(4)受体的高亲和力放射性配体。
Br J Pharmacol. 2000 Jan;129(1):37-46. doi: 10.1038/sj.bjp.0702983.
本文引用的文献
1
Neuropeptide Y-related peptides and their receptors--are the receptors potential therapeutic drug targets?神经肽Y相关肽及其受体——这些受体是潜在的治疗药物靶点吗？
Annu Rev Pharmacol Toxicol. 1993;33:309-52. doi: 10.1146/annurev.pa.33.040193.001521.
2
Modulation of anxiety and neuropeptide Y-Y1 receptors by antisense oligodeoxynucleotides.反义寡脱氧核苷酸对焦虑和神经肽Y-Y1受体的调节作用
Science. 1993 Jan 22;259(5094):528-31. doi: 10.1126/science.8380941.
3
[D-TRP32]neuropeptide Y: a competitive antagonist of NPY in rat hypothalamus.[D-色氨酸32]神经肽Y：大鼠下丘脑神经肽Y的竞争性拮抗剂
J Med Chem. 1994 Mar 18;37(6):811-5. doi: 10.1021/jm00032a015.
4
A role for neuropeptide-Y, dynorphin, and noradrenaline in the central control of food intake after food deprivation.神经肽Y、强啡肽和去甲肾上腺素在食物剥夺后食物摄入的中枢控制中的作用。
Endocrinology. 1993 Jul;133(1):29-32. doi: 10.1210/endo.133.1.8100519.
5
Benextramine-neuropeptide Y receptor interactions: contribution of the benzylic moieties to [3H]neuropeptide Y displacement activity.贝那替秦 - 神经肽Y受体相互作用：苄基部分对[³H]神经肽Y置换活性的贡献。
J Med Chem. 1993 Jan 22;36(2):272-9. doi: 10.1021/jm00054a012.
6
Nonpeptide peptidomimetic antagonists of the neuropeptide Y receptor: benextramine analogs with selectivity for the peripheral Y2 receptor.神经肽Y受体的非肽类拟肽拮抗剂：对外周Y2受体具有选择性的苄苯二胺类似物。
J Med Chem. 1994 Jul 8;37(14):2242-8. doi: 10.1021/jm00040a018.
7
Structure-activity relationships of neuropeptide Y analogues with respect to Y1 and Y2 receptors.神经肽Y类似物相对于Y1和Y2受体的构效关系。
Biopolymers. 1995;37(2):123-42. doi: 10.1002/bip.360370207.
8
Novel modified carboxy terminal fragments of neuropeptide Y with high affinity for Y2-type receptors and potent functional antagonism at a Y1-type receptor.对Y2型受体具有高亲和力且对Y1型受体具有强效功能拮抗作用的新型神经肽Y修饰羧基末端片段。
J Med Chem. 1995 Mar 31;38(7):1150-7. doi: 10.1021/jm00007a012.
9
The first highly potent and selective non-peptide neuropeptide Y Y1 receptor antagonist: BIBP3226.首个高效且选择性的非肽类神经肽Y Y1受体拮抗剂：BIBP3226。
Eur J Pharmacol. 1994 Dec 27;271(2-3):R11-3. doi: 10.1016/0014-2999(94)90822-2.
10
Neuropeptide Y--a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide.神经肽Y——一种与肽YY和胰多肽结构相似的新型脑肽。
Nature. 1982 Apr 15;296(5858):659-60. doi: 10.1038/296659a0.
Zotero 插件