使用[125I]-[赖氨酸5，酪氨酸（碘代2）7，甲基亮氨酸9，正亮氨酸10]-神经激肽A（4-10），通过结合和功能研究获得豚鼠气道中速激肽NK-2受体的证据。

Evidence for tachykinin NK-2 receptors in guinea-pig airways from binding and functional studies, using [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10).

作者信息

Zeng X P, Lavielle S, Burcher E

机构信息

School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia.

出版信息

Neuropeptides. 1994 Jan;26(1):1-9. doi: 10.1016/0143-4179(94)90086-8.

DOI:10.1016/0143-4179(94)90086-8

PMID:7512696

Abstract

The potent contractile responses of guinea-pig airways to neurokinin A (NKA) and neuropeptide gamma (NP gamma) are thought to be mediated by NK-2 receptors. However, NK-2 binding sites are not detectable using the radioligand [125I]-iodohistidyl-NKA. Here, a novel, highly selective iodinated radioligand, [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10), and a number of related peptides have been used to characterize NK-2 receptors on guinea-pig airways, using binding and functional studies. Specific binding of [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10), was saturable and to a single high affinity site, with KD 1.29 +/- 0.36 nM (n = 4). The rank order of potency for tachykinins and analogues as competitors for the binding was: [Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10) > or = NP gamma > or = [Lys5,MeLeu9,Nle10]-NKA(4-10) > NKA > or = SR 48968 >> MDL 29913 > or = substance P (SP) = [127I]-Bolton-Hunter NKA (BHNKA) > or = MEN 10207 > neurokinin B (NKB). Septide, [DPro9,Pro10,Trp11]-SP, the NK-1 selective ligands [Sar9,Met(O2)11]-SP, [Pro9]-SP and CP 96345, the NK-3 selective senktide, and calcitonin gene-related peptide (CGRP) were weak or ineffective. On guinea-pig isolated bronchi, the potency order of contractile agonists was: [Lys5,MeLeu9,Nle10]-NKA(4-10) > NKA > or = NP gamma > or = [Lys5,Tyr7,MeLeu9, Nle10]-NKA(4-10) > or = septide = BHNKA > or = [Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10) > or = [Sar9,Met(O2)11]-SP > or = NKB = [Pro9]-SP > or = SP >> senktide.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

豚鼠气道对神经激肽A（NKA）和神经肽γ（NPγ）的强烈收缩反应被认为是由NK - 2受体介导的。然而，使用放射性配体[125I] - 碘组氨酰 - NKA无法检测到NK - 2结合位点。在此，一种新型的、高度选择性的碘化放射性配体[125I] - [Lys5，Tyr(I2)7，MeLeu9，Nle10] - NKA(4 - 10)以及一些相关肽已被用于通过结合和功能研究来表征豚鼠气道上的NK - 2受体。[125I] - [Lys5，Tyr(I2)7，MeLeu9，Nle10] - NKA(4 - 10)的特异性结合是可饱和的，且作用于单一高亲和力位点，解离常数KD为1.29±0.36 nM（n = 4）。速激肽及其类似物作为结合竞争剂的效价顺序为：[Lys5，Tyr(I2)7，MeLeu9，Nle10] - NKA(4 - 10)≥NPγ≥[Lys5，MeLeu9，Nle10] - NKA(4 - 10)＞NKA≥SR 48968＞＞MDL 29913≥P物质（SP）=[127I] - 博尔顿 - 亨特NKA（BHNKA）≥MEN 10207＞神经激肽B（NKB）。七肽、[DPro9，Pro10，Trp11] - SP、NK - 1选择性配体[Sar9，Met(O2)11] - SP、[Pro9] - SP和CP 96345、NK - 3选择性的速激肽以及降钙素基因相关肽（CGRP）作用较弱或无效。在豚鼠离体支气管上，收缩激动剂的效价顺序为：[Lys5，MeLeu9，Nle10] - NKA(4 - 10)＞NKA≥NPγ≥[Lys5，Tyr7，MeLeu9，Nle10] - NKA(4 - 10)≥七肽=BHNKA≥[Lys5，Tyr(I2)7，MeLeu9，Nle10] - NKA(4 - 10)≥[Sar9，Met(O2)11] - SP≥NKB=[Pro9] - SP≥SP＞＞速激肽。（摘要截短于250字）