Nad - 299可拮抗克隆的5 - HT1A受体中5 - 羟色胺刺激的和螺哌隆抑制的[35S]GTPγS结合。
Nad-299 antagonises 5-HT-stimulated and spiperone-inhibited [35S]GTPgammaS binding in cloned 5-HT1A receptors.
作者信息
Jerning Eva, Rosqvist Susanne, Mohell Nina
机构信息
Department of Lead Discovery, AstraZeneca R&D Södertälje, Novum, Hälsovägen 7, S-141 57 Huddinge, Sweden.
出版信息
J Recept Signal Transduct Res. 2002 Feb-Nov;22(1-4):483-95. doi: 10.1081/rrs-120014616.
In Chinese Hamster Ovary (CHO) cells expressing cloned human 5-hydroxytryptamine1A A (5-HT1A) receptors, (R)-3-N,N-dicyclobutylamino-8-fluoro-[6-3H]-3,4-dihydro-2H-1-benzopyan-5-carboxamide ([3H]NAD-299) exhibited high affinity (Kd = 0.16 nM) and labeled 34% more receptors than 8-hydroxy-2-([2,3-3H]di-n-propylamino)tetralin ([3H]8-OH-DPAT). NAD-299 behaved as a silent antagonist in [35S]GTPgammaS binding similar to N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide (WAY-100635) and (S)-5-fluoro-8-hydroxy-2-(di-n-propylamino)tetralin ((S)UH-301). 5-HT and 5-carboxamidotryptamine (5-CT) stimulated [35S]GTPgammaS binding 2.5-fold while spiperone and methiothepin inhibited [35S]GTPgammaS binding 1.4-fold. Furthermore, NAD-299 antagonised both the 5-HT stimulated and the spiperone inhibited [35S]GTPgammaS binding to basal levels. The KiL/KiH ratios for spiperone (0.66), methiothepin (0.39), WAY-100635 (0.32), (S)UH-301 (0.94), NAD-299 (1.29), NAN-190 (1.23), (S)pindolol (5.85), ipsapirone (13.1), buspirone (24.6), (+/-)8-OH-DPAT (47.3), flesinoxan (55.8), 5-HT (200) and 5-CT (389) correlated highly significantly with the intrinsic activity obtained with [35S] GTPgammaS (r = 0.97).
在表达克隆的人5-羟色胺1A A（5-HT1A）受体的中国仓鼠卵巢（CHO）细胞中，（R）-3-N，N-二环丁基氨基-8-氟-[6-3H]-3,4-二氢-2H-1-苯并吡喃-5-甲酰胺（[3H]NAD-299）表现出高亲和力（Kd = 0.16 nM），并且比8-羟基-2-（[2,3-3H]二正丙基氨基）四氢萘（[3H]8-OH-DPAT）标记的受体多34%。NAD-299在[35S]GTPγS结合中表现为沉默拮抗剂，类似于N-叔丁基-3-（4-（2-甲氧基苯基）-哌嗪-1-基）-2-苯基丙酰胺（WAY-100635）和（S）-5-氟-8-羟基-2-（二正丙基氨基）四氢萘（（S）UH-301）。5-羟色胺（5-HT）和5-羧酰胺色胺（5-CT）刺激[35S]GTPγS结合2.5倍，而螺哌隆和甲硫哒嗪抑制[35S]GTPγS结合1.4倍。此外，NAD-299将5-HT刺激的和螺哌隆抑制的[35S]GTPγS结合都拮抗至基础水平。螺哌隆（0.66）、甲硫哒嗪（0.39）、WAY-100635（0.32）、（S）UH-301（0.94）、NAD-299（1.29）、NAN-190（1.23）、（S）吲哚洛尔（5.85）、伊沙匹隆（13.1）、丁螺环酮（24.6）、（±）8-OH-DPAT（47.3）、氟司立辛（55.8）、5-HT（200）和5-CT（389）的KiL/KiH比值与用[35S]GTPγS获得的内在活性高度显著相关（r = 0.97）。
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