[3H]spiroxatrine: a 5-HT1A radioligand with agonist binding properties.
[3H]spiroxatrine: a 5-HT1A radioligand with agonist binding properties.
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[3H]spiroxatrine：一种具有激动剂结合特性的 5-HT1A 放射性配体。
DOI：
10.1111/j.1471-4159.1988.tb02943.x
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发表时间：
1988
影响因子：
4.7
通讯作者：
Titeler,M
中科院分区：
文献类型：
--
作者：
Herrick-Davis,K;Titeler,M
据报道，Spiroxatrine是一种5-HT 1A血清素受体拮抗剂。因此，[3 H]spiroxatrine的合成和其在大鼠海马膜匀浆中的5-HT 1A受体结合特性进行了表征，期望它将是第一个5-HT 1A拮抗剂放射性配体。[3H]8平行研究了一种充分表征的5-HT 1A激动剂放射性配体-羟基二丙氨基四氢化萘（[3 H]8-OH-DPAT），以进行比较。Scatchard分析[3 H]spiroxatrine和[3 H]8-OH-DPAT结合饱和度的研究，得出的KD值分别为0.9 nAf和1.8 nM，Bmax值分别为424和360 fmol/mg蛋白。一系列药物在竞争[3 H]-螺沙嘌呤和[3 H]8-OH-DPAT结合时获得的K1值之间存在高度显著的相关性（r= 0.98; p < 0.001）。特别值得注意的是，观察到5-HT 1A激动剂（如5-羟色胺、8-OH-DPAT和伊沙匹隆）与[3 H]螺沙丁胺或[3 H]8-OH-DPAT-标记的5-HT 1A受体具有相同的高亲和力。5′-（β，γ-亚氨基）三磷酸鸟苷（一种GTP的不可水解类似物）以浓度依赖性方式抑制[3 H]Spiroxatrine和[3 H]8-OH-DPAT与5-HT 1A受体的结合，而5′-（β，γ-亚氨基）三磷酸腺苷（一种ATP的不可水解类似物）则无此作用。[3 H]-螺沙丁胺和[3 H]8-OH-DPAT的5-HT 1A受体放射性标记特性相似，即，激动剂的高亲和力和鸟苷酸敏感性表明，[3 H]螺沙丁胺在与5-HT 1A受体的相互作用中具有“激动剂样”结合特性。
Spiroxatrine has been reported to be a 5‐HT1Aserotonin receptor antagonist. Therefore [3H]spiroxatrine was synthesized and its 5‐HT1Areceptor binding properties in homogenates of rat hippocampal membranes were characterized with the expectation that it would be the first 5‐HT1Aantagonist radioligand. [3H]8‐Hydroxydipropylaminotetralin ([3H]8‐OH‐DPAT), a well‐characterized 5‐HT1Aagonist radioligand, was studied in parallel for comparative purposes. Scatchard analyses of saturation studies of [3H]spiroxatrine and [3H]8‐OH‐DPAT binding producedKDvalues of 0.9 nAf and 1.8 nM, withBmaxvalues of 424 and 360 fmol/mg protein, respectively. A highly significant correlation (r= 0.98; p < 0.001) exists betweenK1values obtained for a series of drugs in competing for [3H]‐spiroxatrine and [3H]8‐OH‐DPAT binding. Of special interest was the observation that 5‐HT1Aagonists such as serotonin, 8‐OH‐DPAT, and ipsapirone competed with equal high affinities for [3H]spiroxatrine or [3H]8‐OH‐DPAT‐labelled 5‐HT1Areceptors. [3H]Spiroxatrine and [3H]8‐OH‐DPAT binding to 5‐HT1Areceptors was inhibited by guanosine 5′‐(β,γ‐imido)triphosphate (a nonhydrolyzable analog of GTP) in a concentration‐dependent manner whereas adenosine 5′‐(β,γ‐imido)triphosphate (a non‐hydrolyzable analog of ATP) had no effect. The similarities in the 5‐HT1Areceptor radiolabelling properties of [3H]‐spiroxatrine and [3H]8‐OH‐DPAT, i.e., the high affinities of agonists and the guanyl nucleotide sensitivity, indicate that [3H]spiroxatrine has “agonist‐like” binding properties in its interaction with the 5‐HT1Areceptor.