新型选择性放射性配体[125I][赖氨酸5，酪氨酸（碘2）7，甲基亮氨酸9，正亮氨酸10]神经激肽A-（4-10）对大鼠胃底速激肽NK2受体的表征

Characterisation of a novel, selective radioligand, [125I][Lys5,Tyr(I2)7,MeLeu9,Nle10]neurokinin A-(4-10), for the tachykinin NK2 receptor in rat fundus.

作者信息

Burcher E, Badgery-Parker T, Zeng X P, Lavielle S

机构信息

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

出版信息

Eur J Pharmacol. 1993 Mar 23;233(2-3):201-7. doi: 10.1016/0014-2999(93)90051-i.

DOI:10.1016/0014-2999(93)90051-i

PMID:8385622

Abstract

The tyrosyl derivative of the tachykinin NK2 selective agonist [Lys5,MeLeu9,Nle10]NKA-(4-10) was iodinated and the product [125I][Lys5,Tyr(I2)2,MeLeu9,Nle10]NKA-(4-10) purified using reverse phase HPLC. The binding characteristics of this novel radioligand were investigated in homogenates of rat gastric fundus. Binding was saturable, reversible and to a single population of high affinity sites of KD 1.3 +/- 0.2 nM (n = 4). Specific binding of [125I][Lys5,Tyr(I2)7,MeLeu9,Nle10]NKA-(4-10) was inhibited by neuropeptide gamma SR 48968 > or = neurokinin A (NKA) > or = [Lys5,MeLeu9,Nle10]NKA-(4-10) > [Lys5,Tyr7,MeLeu9,Nle10] NKA-(4-10) > neuropeptide K > [Lys5,Tyr(I2)7,MeLeu9,Nle10]NKA-(4-10) > MDL 29,913 > [127I]- Bolton-Hunter-NKA > neurokinin B > substance P (SP) >> MEN 10207 > [Sar9,Met(O2)11]SP >> senktide, indicating binding to NK2 receptors. NKA, [Lys5,MeLeu9,Nle10]NKA-(4-10) and [Lys5,Tyr(I2)7,MeLeu9,Nle10]NKA-(4-10) contracted the isolated fundus strip, with pD2 values 7.9, 7.7 and 7.4, respectively. This novel, highly selective radioligand should prove useful in characterisation studies in peripheral tissues.

摘要

速激肽NK2选择性激动剂[Lys5,MeLeu9,Nle10]NKA-(4 - 10)的酪氨酰衍生物被碘化，产物[125I][Lys5,Tyr(I2)2,MeLeu9,Nle10]NKA-(4 - 10)采用反相高效液相色谱法进行纯化。在大鼠胃底匀浆中研究了这种新型放射性配体的结合特性。结合是可饱和的、可逆的，且针对单一群体的高亲和力位点，解离常数KD为1.3±0.2 nM（n = 4）。[125I][Lys5,Tyr(I2)7,MeLeu9,Nle10]NKA-(4 - 10)的特异性结合被神经肽γ、SR 48968≥神经激肽A（NKA）≥[Lys5,MeLeu9,Nle10]NKA-(4 - 10)>[Lys5,Tyr7,MeLeu9,Nle10] NKA-(4 - 10)>神经肽K>[Lys5,Tyr(I2)7,MeLeu9,Nle10]NKA-(4 - 10)>MDL 29,913>[127I]-博尔顿-亨特-NKA>神经激肽B>P物质（SP）>>MEN 10207>[Sar9,Met(O2)11]SP>>森克肽抑制，表明其与NK2受体结合。NKA、[Lys5,MeLeu9,Nle10]NKA-(4 - 10)和[Lys5,Tyr(I2)7,MeLeu9,Nle10]NKA-(4 - 10)使离体胃底条收缩，pD2值分别为7.9、7.7和7.4。这种新型、高选择性的放射性配体在周围组织的特性研究中应会证明是有用的。