FR 113680：一种具有NK1受体选择性的新型三肽P物质拮抗剂。
FR 113680: a novel tripeptide substance P antagonist with NK1 receptor selectivity.
作者信息
Morimoto H, Murai M, Maeda Y, Hagiwara D, Miyake H, Matsuo M, Fujii T
机构信息
Department of Pharmacology, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan.
出版信息
Br J Pharmacol. 1992 May;106(1):123-6. doi: 10.1111/j.1476-5381.1992.tb14303.x.
Abstract
- We have discovered a novel tripeptide substance P (SP) antagonist, FR 113680 [N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N'-formyl-D- tryptophyl]-N-methyl-N-phenylmethyl-L-phenylalaninamide]. In binding experiments, FR 113680 inhibited [3H]-SP binding to guinea-pig lung membranes (NK1) in a competitive manner but had not effect on [3H]-SP binding to rat cerebral cortical membranes (NK1), [3H]-neurokinin A ([3H]-NKA) binding to rat duodenum smooth muscle membranes (NK2) and [3H]-eledoisin (Ele) binding to rat cerebral cortical membranes (NK3). 2. In bioassay experiments, FR 113680 dose-dependently inhibited SP-induced guinea-pig ileum contraction (NK1), but did not inhibit either NKA-induced rat vas deferens contraction (NK2) or neurokinin B (NKB)-induced contraction of rat portal vein (NK3). According to Schild plot analysis, the inhibitory effect of FR 113680 on SP-induced guinea-pig ileum contraction is competitive and the pA2 value is 7.53. 3. The inactivity of FR 113680 on NK1 receptors in rat compared to guinea-pig may represent species-specific forms of the NK1 receptor. 4. These findings suggest that FR 113680 interacts selectively with the NK1 neurokinin receptor.
摘要
- 我们发现了一种新型三肽物质P（SP）拮抗剂，FR 113680 [Nα-[Nα-(Nα-乙酰基-L-苏氨酰基)-N'-甲酰基-D-色氨酰基]-N-甲基-N-苯基甲基-L-苯丙氨酰胺]。在结合实验中，FR 113680以竞争性方式抑制[3H]-SP与豚鼠肺膜（NK1）的结合，但对[3H]-SP与大鼠大脑皮层膜（NK1）的结合、[3H]-神经激肽A（[3H]-NKA）与大鼠十二指肠平滑肌膜（NK2）的结合以及[3H]-伊来多辛（Ele）与大鼠大脑皮层膜（NK3）的结合均无影响。2. 在生物测定实验中，FR 113680剂量依赖性地抑制SP诱导的豚鼠回肠收缩（NK1），但不抑制NKA诱导的大鼠输精管收缩（NK2）或神经激肽B（NKB）诱导的大鼠门静脉收缩（NK3）。根据Schild图分析，FR 113680对SP诱导的豚鼠回肠收缩的抑制作用具有竞争性，pA2值为7.53。3. 与豚鼠相比，FR 113680对大鼠NK1受体无活性可能代表NK1受体的物种特异性形式。4. 这些发现表明FR 113680与NK1神经激肽受体选择性相互作用。
相似文献
1
FR 113680: a novel tripeptide substance P antagonist with NK1 receptor selectivity.FR 113680：一种具有NK1受体选择性的新型三肽P物质拮抗剂。
Br J Pharmacol. 1992 May;106(1):123-6. doi: 10.1111/j.1476-5381.1992.tb14303.x.
2
FK 224, a novel cyclopeptide substance P antagonist with NK1 and NK2 receptor selectivity.FK 224，一种对NK1和NK2受体具有选择性的新型环肽物质P拮抗剂。
J Pharmacol Exp Ther. 1992 Jul;262(1):398-402.
3
Novel selective agonists and antagonists confirm neurokinin NK1 receptors in guinea-pig vas deferens.新型选择性激动剂和拮抗剂证实了豚鼠输精管中的神经激肽NK1受体。
Br J Pharmacol. 1991 Feb;102(2):511-7. doi: 10.1111/j.1476-5381.1991.tb12202.x.
4
Pharmacological profile of a high affinity dipeptide NK1 receptor antagonist, FK888.高亲和力二肽NK1受体拮抗剂FK888的药理学特性
Br J Pharmacol. 1992 Nov;107(3):785-9. doi: 10.1111/j.1476-5381.1992.tb14524.x.
5
Pharmacological analysis of [3H]-senktide binding to NK3 tachykinin receptors in guinea-pig ileum longitudinal muscle-myenteric plexus and cerebral cortex membranes.[3H] - 速激肽与豚鼠回肠纵肌 - 肠肌间神经丛及大脑皮层膜中NK3速激肽受体结合的药理学分析
Br J Pharmacol. 1990 Apr;99(4):767-73. doi: 10.1111/j.1476-5381.1990.tb13004.x.
6
A pharmacological study of NK1 and NK2 tachykinin receptor characteristics in the rat isolated urinary bladder.大鼠离体膀胱中NK1和NK2速激肽受体特性的药理学研究
Br J Pharmacol. 1992 Nov;107(3):777-84. doi: 10.1111/j.1476-5381.1992.tb14523.x.
7
Characterization of NK1 and NK2 tachykinin receptors in guinea-pig and rat bronchopulmonary and vascular systems.豚鼠和大鼠支气管肺及血管系统中NK1和NK2速激肽受体的特性研究
Br J Pharmacol. 1994 Mar;111(3):759-68. doi: 10.1111/j.1476-5381.1994.tb14803.x.
8
Pharmacological properties of a potent and selective nonpeptide substance P antagonist.一种强效且选择性的非肽类P物质拮抗剂的药理特性。
Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10208-12. doi: 10.1073/pnas.88.22.10208.
9
Tachykinin receptors in smooth muscles: a study with agonists (substance P, neurokinin A) and antagonists.平滑肌中的速激肽受体：一项使用激动剂（P物质、神经激肽A）和拮抗剂的研究。
Eur J Pharmacol. 1985 Nov 26;118(1-2):25-36. doi: 10.1016/0014-2999(85)90659-4.
10
Characterization of receptors mediating contraction induced by tachykinins in the guinea-pig isolated common bile duct.豚鼠离体胆总管中速激肽介导收缩的受体特性研究
Br J Pharmacol. 1997 Dec;122(8):1633-8. doi: 10.1038/sj.bjp.0701560.
引用本文的文献
1
Characterization of NK1 and NK2 tachykinin receptors in guinea-pig and rat bronchopulmonary and vascular systems.豚鼠和大鼠支气管肺及血管系统中NK1和NK2速激肽受体的特性研究
Br J Pharmacol. 1994 Mar;111(3):759-68. doi: 10.1111/j.1476-5381.1994.tb14803.x.
2
Pharmacological profile of a high affinity dipeptide NK1 receptor antagonist, FK888.高亲和力二肽NK1受体拮抗剂FK888的药理学特性
Br J Pharmacol. 1992 Nov;107(3):785-9. doi: 10.1111/j.1476-5381.1992.tb14524.x.
本文引用的文献
1
Protein measurement with the Folin phenol reagent.使用福林酚试剂进行蛋白质测定。
J Biol Chem. 1951 Nov;193(1):265-75.
2
Some quantitative uses of drug antagonists.药物拮抗剂的一些定量应用。
Br J Pharmacol Chemother. 1959 Mar;14(1):48-58. doi: 10.1111/j.1476-5381.1959.tb00928.x.
3
Undeca- and octa-peptide antagonists for substance P, a study on the guinea pig trachea.用于P物质的十一肽和八肽拮抗剂：豚鼠气管研究
Eur J Pharmacol. 1984 Mar 23;99(2-3):193-202. doi: 10.1016/0014-2999(84)90241-3.
4
Substance P.P物质
Pharmacol Rev. 1983 Jun;35(2):85-141.
5
3h-substance P binding to salivary gland membranes. Regulation by guanyl nucleotides and divalent cations.
Mol Pharmacol. 1983 May;23(3):563-9.
6
Capsaicin-induced desensitization of airway mucosa to cigarette smoke, mechanical and chemical irritants.辣椒素诱导气道黏膜对香烟烟雾、机械和化学刺激物产生脱敏作用。
Nature. 1983;302(5905):251-3. doi: 10.1038/302251a0.
7
Gamma-aminobutyric acid binding to receptor sites in the rat central nervous system.γ-氨基丁酸与大鼠中枢神经系统中的受体位点结合。
Proc Natl Acad Sci U S A. 1974 Dec;71(12):4802-7. doi: 10.1073/pnas.71.12.4802.
8
The binding of [3H]leukotriene C4 to guinea-pig lung membranes. The lack of correlation of LTC4 functional activity with binding affinity.
Eur J Pharmacol. 1987 Nov 17;143(3):323-34. doi: 10.1016/0014-2999(87)90456-0.
9
The rat isolated portal vein: a preparation sensitive to neurokinins, particularly neurokinin B.大鼠离体门静脉：一种对神经激肽，尤其是神经激肽B敏感的标本。
Eur J Pharmacol. 1987 Feb 24;134(3):321-6. doi: 10.1016/0014-2999(87)90363-3.
10
Peripheral effects of neurokinins: functional evidence for the existence of multiple receptors.神经激肽的外周效应：多种受体存在的功能证据
J Auton Pharmacol. 1987 Mar;7(1):11-32. doi: 10.1111/j.1474-8673.1987.tb00130.x.
Zotero 插件