AUTORADIOGRAPHIC CHARACTERIZATION AND LOCALIZATION OF 5-HT(1D) COMPARED TO 5-HT(1B) BINDING-SITES IN RAT-BRAIN
AUTORADIOGRAPHIC CHARACTERIZATION AND LOCALIZATION OF 5-HT(1D) COMPARED TO 5-HT(1B) BINDING-SITES IN RAT-BRAIN
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DOI：
10.1007/bf00166939
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发表时间：
1993-06-01
影响因子：
3.6
通讯作者：
HOYER, D
中科院分区：
文献类型：
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作者：
BRUINVELS, AT;PALACIOS, JM;HOYER, D
用放射自显影技术测定了新型5-羟色胺(5-羟色胺)5-羟色胺(5-HT1B/1D)选择性放射性配基serotonin-O-carboxy-methyl-glycyl-[I-125]tyrosinamide(简记为[I-125]GTI)标记的结合部位在大鼠脑内的区域分布和药理作用。[I-125]GTI结合位点的分布与标记5-HT1B结合位点的[I-125]碘氰基吲哚([I-125]ICYP)的分布基本相似，[I-125]ICYP标记5-HT1B结合位点(在8-OH-DPAT(8-羟基-[2N-二丙氨基]四氢)和异丙肾上腺素的存在下，防止与5-HT1A和β-肾上腺素受体结合位点的结合)，尽管详细的分析表明不同。[I-125]GTI结合位点的药理分析使用已知的与5-HT1B和/或区分5-HT1B和5-HT1D位点的化合物：5-氨基色胺(5-CT)舒马曲普坦，CP 93129(5-hydroxy-3(4-1，2，5，6-tetrahydropyridyl)-4-azaindole)，(-)吲哚酚，PAPP(4[2-[4-[3-(三氟甲基)苯基]-1-哌嗪基]乙基]苯甲胺)，萝卜素，和8-羟基-DPAT。5-CT对[I-125]GTI的位移为单相。相反，选择性5-羟色胺1B化合物CP 93129和(-)吲哚洛尔产生的双相曲线显示苍白球和黑质中的大多数高亲和力部位，而Papp和舒马曲坦(对5-羟色胺1D有一定的选择性)则产生双相曲线，显示这些区域有少数高亲和力部位。此外，通过用100 nM CP 93129封闭5-HT1B位点，可以研究剩余的[I-125]GTI结合位点群，并发现它们对PAPP、Rauwolscine和8-OH-DPAT具有很高的亲和力。主要结合组分的药理图谱是典型的5-HT1B型：5-CT>；CP 93129大于或等于(-)吲哚洛尔；舒马曲坦大于或等于Papp>；rauwolscine。[I-125]GTI结合的次要成分的图谱最好地表征为5-HT1D位点：5-CT&>PAPP大于或等于Sumtriptan；rauwolscine>；(-)inddolol大于或等于CP 93129。非5-HT1B[I-125]GTI结合位点的定位特征是用100 nM CP 93129阻断5-HT1B受体。5-HT1D识别位点在苍白球、苍白球腹侧、尾壳核、丘脑底核、内侧丘脑核、黑质(网状部)、视束核(正常核和副核)、膝状体不同核和额顶皮质均有较高密度的5-HT1D识别位点。因此，与最近克隆的大鼠5-HT1Dalpha受体基因的克隆一致，可以证明5-HT1D位点在大鼠脑内的存在和分布。然而，与5-HT1B位点相比，5-HT1D位点仅代表所研究的大鼠脑结构中[I-125]GTI结合的一小部分。
The regional distribution and the pharmacology of the binding sites labelled with the novel 5-hydroxytryptamine (serotonin) 5-HT1B/1D selective radioligand serotonin-O-carboxy-methyl-glycyl-[I-125]tyrosinamide (abbreviated [I-125]GTI for the sake of simplicity) was determined using quantitative autoradiography in rat brain. The distribution of [I-125]GTI binding sites was largely comparable to that of [I-125]iodocyanopindolol ([I-125] ICYP) which labels 5-HT1B binding sites (in the presence of 8-OH-DPAT (8-hydroxy-[2N-dipropylamino]tetralin) and isoprenaline, to prevent binding to 5-HT1A and beta-adrenoceptor binding sites), although a detailed analysis revealed differences.The pharmacology of the [I-125]GTI binding sites was analysed using compounds known to display high affinity for and/or distinguish between 5-HT1B and 5-HT1D sites: 5-carboxamidotryptamine (5-CT), sumatriptan, CP 93129 (5-hydroxy-3(4-1,2,5,6-tetrahydropyridyl)-4-azaindole), (-)pindolol, PAPP (4[2-[4-[3-(trifluoromethyl) phenyl]-1-piperazinyl]ethyl]benzeneamine), rauwolscine, and 8-OH-DPAT. The displacement of [I-125]GTI by 5-CT was monophasic. By contrast, the selective 5-HT1B compound CP 93129 and (-)pindolol produced biphasic curves showing a majority of high affinity sites in the globus pallidus and the substantia nigra, whereas PAPP and sumatriptan (which are somewhat 5-HT1D selective) produced biphasic curves indicating a minority of high affinity sites in these areas. In addition, by blocking the 5-HT1B sites with 100 nM CP 93129, the remaining population of [I-125]GTI binding sites could be studied and was found to have high affinity for PAPP, rauwolscine and 8-OH-DPAT. The pharmacological profile of the major binding component was typical of the 5-HT1B type: 5-CT>CP 93129 greater-than-or-equal-to (-)pindolol>sumatriptan greater-than-or-equal-to PAPP >rauwolscine. The profile of the minor component of [I-125]GTI binding is best characterised as that of a 5-HT1D site: 5-CT>PAPP greater-than-or-equal-to sumatriptan>rauwolscine > (-)pindolol greater-than-or-equal-to CP 93129.The localisation of the non 5-HT1B [I-125]GTI binding sites was characterised by blocking the 5-HT1B receptors with 100 nM CP 93129. Low densities of the 5-HT1D recognition sites were found to be present in globus pallidus, ventral pallidum, caudate-putamen, subthalamic nucleus, entopeduncular nucleus, substantia nigra (reticular part), nuclei of the (normal and accessory) optic tract, different nuclei of the geniculate body and frontoparietal cortex, although higher densities of 5-HT1B sites were always observed in the same structures. Thus, in agreement with the recent cloning of a rat 5-HT1Dalpha receptor cDNA, the presence and the distribution of 5-HT1D sites could be documented in rat brain. However, when compared to 5-HT1B sites, 5-HT1D sites represent only a minor component of the [I-125]GTI binding in the rat brain structures studied.