[125I]碘博来胺，一种用于豚鼠脑内组胺H1受体的高灵敏度探针。

[125I]Iodobolpyramine, a highly sensitive probe for histamine H1-receptors in guinea-pig brain.

作者信息

Korner M, Bouthenet M L, Ganellin C R, Garbarg M, Gros C, Ife R J, Sales N, Schwartz J C

出版信息

Eur J Pharmacol. 1986 Jan 21;120(2):151-60. doi: 10.1016/0014-2999(86)90535-2.

Abstract

[125I]Iodobolpyramine is a novel 125I-ligand for histamine H1-receptors, synthesised using the 125I-Bolton Hunter reagent (2000 Ci/mmol) for acylation of an aminopentyl analogue of mepyramine. Its specific binding varied linearly with the concentration of guinea-pig cerebellar membranes and represented about 80% of the total. Selective interaction with H1-receptors was demonstrated by estimation of Ki values of known agonists and antagonists and confirmed by the low affinity of histamine H2- and H3-receptor antagonists and of non-histaminergic agents. At 25 degrees C, [125I]iodobolpyramine exhibited a slow association rate (180-240 min to reach equilibrium) and a slow dissociation rate (t1/2 = 201 min). Kinetic and saturation data yielded KD values of 0.05 and 0.15 nM, respectively, indicating that it is among the most potent H1-receptor antagonists known. The sensitivity for detecting H1-receptors in guinea-pig cerebellum using [125I]iodobolpyramine was increased 50-fold relative to use of [3H]mepyramine. Well-contrasted autoradiograms of guinea-pig brain, obtained after a short exposure time, confirmed previous H1-receptor localisation established with [3H]mepyramine and revealed new localisations, e.g. in cerebral cortex and nucleus accumbens.

摘要

[125I]碘博尔吡胺是一种新型的组胺H1受体125I配体，它是使用125I-博尔顿·亨特试剂（2000 Ci/mmol）对美吡拉敏的氨基戊基类似物进行酰化反应合成的。其特异性结合与豚鼠小脑膜浓度呈线性变化，约占总量的80%。通过估算已知激动剂和拮抗剂的Ki值证明了与H1受体的选择性相互作用，并通过组胺H2和H3受体拮抗剂以及非组胺能药物的低亲和力得到证实。在25℃时，[125I]碘博尔吡胺表现出缓慢的结合速率（达到平衡需180 - 240分钟）和缓慢的解离速率（t1/2 = 201分钟）。动力学和饱和数据分别得出KD值为0.05和0.15 nM，表明它是已知最强效的H1受体拮抗剂之一。与使用[3H]美吡拉敏相比，使用[125I]碘博尔吡胺检测豚鼠小脑中H1受体的灵敏度提高了50倍。在短曝光时间后获得的豚鼠脑对比度良好的放射自显影片，证实了先前用[3H]美吡拉敏确定的H1受体定位，并揭示了新的定位，例如在大脑皮层和伏隔核。