哺乳动物中枢两种不同的5-羟色胺受体

用放射配基结合分析等方法证明,哺乳动物中枢,带氚标记的5-羟色胺(5-HT)和螺哌啶,分别标记在两种不同性质的5-HT受体上,Peroutka和Snyder把这两种亚型受体分别称为5-HT_1受体和5-HT_2受体。一般说来,5-HT_1受体对5-HT及其受体激动剂敏感;5-HT_2受体对受体拮抗剂敏感,但对5-HT是低敏感的。这两种亚型受体的中枢分布及其生理学意义已作了初步探讨。最近,根据电生理等实验观察表明,中脑中缝核存在5-HT自身受体。有学者提出,5-HT_1受体还可再分为两种亚型。提示存在多种亚型5-HT受体的可能性。     

咪唑啉受体研究进展

本文简述了人们对咪唑啉（Ｉ）受体及其内源性配体的认识过程。Ｉ受体主要分布于脑内,其作用广泛,以调节交感神经张力为主。Ｉ受体可分Ｉ１受体和Ｉ２受体两型。Ｉ１和Ｉ２受体的氨基酸序列和第二信使尚不清楚。胍基丁胺是Ｉ受体的内源性配体,分布较广泛,有多种生物学作用。第二代中枢降压药莫索尼定、雷美尼定对Ｉ１受体的亲和力较高,中枢抑制等副作用较弱。     

甘丙肽受体的研究进展

目前已经克隆了3种甘丙肽受体（GalR1, GalR2, GalR3）,它们都是与G蛋白相偶联的受体.3种甘丙肽受体的氨基酸序列、药理学特性以及第二信使系统各不相同.GalR1/3受体可以抑制腺苷酸环化酶并可以激活钾通道,GalR2受体可以激活磷脂酶C并增加胞内钙离子浓度.用RNA印迹、反转录PCR以及原位杂交等技术对上述3种甘丙肽受体在人、大鼠和小鼠中的分布进行了研究,发现它们具有不同的分布特征,提示不同的甘丙肽受体可能参与不同的生理过程.     

P2Y 受体研究进展

P2受体作为一类核苷酸受体,可分为门控离子通道P2X受体和G蛋白偶联P2Y受体。P2Y受体在人体内分布广泛,功能复杂,迄今为止已从人体组织细胞克隆出9种P2Y受体,分别为P2Y1,2,4,6,11,1,13,14,15受体。本文对P2Y受体的结构特征、生理功能、药理特性和临床应用进行综述。     

基底神经节中多巴胺和腺苷受体二聚化及其药理学意义

近年来,大量研究发现G蛋白偶联受体不仅以单体形式,而且以同源或异源二聚体形式存在。腺苷A1受体和多巴胺D1受体以及腺苷A2a受体和多巴胺D2受体分别共存于基底神经节中纹状体向黑质和脚内核投射的神经元以及纹状体向苍白球投射的神经元内。A1／D1、A2a／D2受体形成受体异聚复合体构成了受体一受体之间相互作用的分子基础。腺苷和多巴胺受体之间在细胞水平以及行为水平上拮抗性的相互作用为其在帕金森病、精神分裂症、舞蹈病和药物依赖等疾病的治疗上提供了新的靶向。     

子宫肌瘤中IGF-1受体的变化及其与雌、孕激素受体、PCNA和Bcl-2的关系

目的观察人子宫肌瘤及周围正常子宫平滑肌组织中IGF-1受体、雌、孕激素受体、PCNA及Bcl-2含量的区别,并分析其相互关系。方法用免疫组化ABC法检测子宫肌瘤及正常子宫平滑肌组织中IGF-1受体、雌、孕激素受体、PCNA及Bcl-2含量,并对其进行图像分析;用SPSS 11统计分析软件对其进行统计及相关性分析。结果子宫肌瘤组织中IGF-1受体的含量明显高于正常子宫平滑肌组织中含量,且与雌、孕激素受体、PCNA及Bcl-2之间均存在显著正相关。结论甾体激素可能通过调节生长因子IGF-1受体含量,调节与细胞增殖相关蛋白的表达以及抑制细胞凋亡等机制,来参与子宫肌瘤的发生发展。     

溶血磷脂酸受体及下游信号通路在心脏细胞生长中的调节作用

溶血磷脂酸（1ysophosphatidic acid,LPA）是一种十分活跃的磷脂信号分子,具有广泛的生物学效应,包括诱导神经轴突回缩、应力纤维形成、促进血小板凝集、诱导平滑肌收缩、刺激血管平滑肌细胞增殖等。LPA通过其受体及耦联的G蛋白调节细胞内信号途径,介导各种生物学效应。心脏组织中存在多种LPA受体亚型,尤其受体LPAl亚型在心脏组织中的含量仅次于脑,位居第二,暗示LPA在心脏中有重要的生物学功能。本文着重对LPA的5种受体亚型的组织分布、与G蛋白的耦联和对第二信使的活性调节,以及LPA及其受体亚型对心脏细胞的生长调节作一综述。     

神经肽Y及其受体Y1、Y2对痛觉调制的研究进展

神经肽Y（neuropeptide Y,NPY）是一种由36个氨基酸残基组成的肽类激素,属胰多肽家族,广泛分布于中枢及外周神经组织的神经元中。NPY主要参与摄食行为、心血管活动、垂体分泌等生理功能的调节。NPY还参与了痛觉调制。NPY受体有Y1、Y2、Y3、Y4、Y5和Y6六种亚型。目前对Y1受体和Y2受体的研究较多,显示Y1受体和Y2受体参与痛觉调制。但现在对NPY在痛觉中的具体作用机制还不清楚。该文对NPY及其Y1受体、Y2受体在痛觉调制中的作用作一概述。     

离子通道受体P2X4的结构及生物学功能

P2X4受体是P2X受体家族的成员。目前,已从人、大鼠、小鼠、鸡胚和非洲爪蟾的组织中获得了全长cDNA。P2X4受体分布广泛,在被ATP及其同系物激活后,引起细胞内钙离子浓度显升高,将信号传递给下游的信号分子。     

5—羟色胺受体的分型,分布和功能

5-HT受体分为5-HT_1、5-HT_2和5-HT_3受体三种亚型。5-HT_1受体又可划分为5-HT_(1A)、5-HT_(1B)、5-HT_(1C)、5-HT_(1D)受体亚亚型;5-HT_3又划分为5-HT_(3S)、5-HT_)3P)、5-HT_(3A)受体亚亚型。5-HT_1受体可能还有新的亚亚型。5-HT受体的上述分型,为解释5-HT的复杂生理、病理生理作用及其某些拮抗效应提供了依据。     

细胞受体与疾病的相关性研究进展

受体是存在于效应细胞中的重要功能蛋白，它和配体具有高亲和力，受体异常亦称受体病，拟就近年来细胞受体和受体病的研究进展作一综述。     

The vitamin D receptor: a primitive steroid receptor related to thyroid hormone receptor

We have previously reported the cloning and sequencing of both the chicken and human vitamin D3 receptor cDNAs. A comparison of their deduced amino acid sequence with that of the other classic steroid hormone receptors and the receptor for thyroid hormone indicates that there are two regions of conservation between these molecules. The first is a 70 amino acid, cysteine-rich sequence (C1), the second region (C2) is a 62 amino acid region located towards the carboxyl terminus of the proteins. In other systems the former has been identified as a region responsible for DNA binding activity, whereas the latter represents the NH2-terminal boundary of the hormone binding domain. We present here evidence utilizing eucaryotic expression of cDNA encoding the hVDR C1 domain, followed by a DNA cellulose chromatography assay, which confirms that the DNA binding activity resides in this region of the receptor for vitamin D3. Additionally, the vitamin D3 receptor contains a 60 amino acid portion at its carboxyl terminus (C3) which exhibits homology with the receptor for thyroid hormone. Conservation in this region of the molecule is found only between homologous or closely related receptors. This indicates a relationship between the vitamin D3 receptor and the receptor for thyroid hormone and may suggest that they evolved from a single primordial gene.     

Nonsteroidal progesterone receptor ligands with unprecedented receptor selectivity

We have characterized a series of nonsteroidal progesterone receptor ligands, the tetrahydropyridazines. Compounds in this series, exemplified by RWJ 26819, demonstrate high affinity and unprecedented specificity for the progesterone receptor relative to other steroid hormone receptors. Like steroidal progestins, RWJ 26819 induces binding of the receptor to a progesterone response element in vitro, and stimulates gene expression in and proliferation of T47D human breast cancer cells. When administered to rabbits orally or subcutaneously, the compound induces histological changes in the uterine lining comparable to those induced by levonorgestrel. It also inhibits ovulation in monkeys. Though less potent in cells and in animal models than would be predicted from binding affinity alone, their enhanced selectivity suggests that they could be effectively used in a clinical setting. Most of the tetrahydropyridazines synthesized are progestin agonists or mixed agonists and antagonists in vitro; however, one compound with antagonist activity in the rabbit uterine transformation assay has been identified.     

褪黑素受体

褪黑素是松果体分泌的主要激素,其功能活动通过特异的Ｇ蛋白耦联受体介导,本文综述褪黑素受体 分布、药理学特性,受体的克隆及受体基因结构特点。     

Dopamine D4 receptor oligomerization--contribution to receptor biogenesis

Dopamine D(4) receptors (D(4) Rs) are G protein-coupled receptors that play a role in attention and cognition. In the present study, we investigated the dimerization properties of this receptor. Western blot analysis of the human D(4.2)R, D(4.4)R and D(4.7)R revealed the presence of higher molecular weight immunoreactive bands, which might indicate the formation of receptor dimers and multimers. Homo- and heterodimerization of the receptors was confirmed by co-immunoprecipitation and bioluminescence resonance energy transfer studies. Although dimerization of a large number of G protein-coupled receptors has been described, the functional importance often remains to be elucidated. Folding efficiency is rate-limiting for D(4)R biogenesis and quality control in the endoplasmic reticulum plays an important role for D(4)R maturation. Co-immunoprecipitation and immunofluorescence microscopy studies using wild-type and a nonfunctional D(4.4)R folding mutant show that oligomerization occurs in the endoplasmic reticulum and that this plays a role in the biogenesis and cell surface targeting of the D(4)R. The different polymorphic repeat variants of the D(4)R display differential sensitivity to the chaperone effect. In the present study, we show that this is also reflected by bioluminescence resonance energy transfer saturation assays, suggesting that the polymorphic repeat variants have different relative affinities to form homo- and heterodimers. In summary, we conclude that D(4)Rs form oligomers with different affinities and that dimerization plays a role in receptor biogenesis.     

Beta-arrestin binding to the beta2-adrenergic receptor requires both receptor phosphorylation and receptor activation

Homologous desensitization of beta2-adrenergic receptors has been shown to be mediated by phosphorylation of the agonist-stimulated receptor by G-protein-coupled receptor kinase 2 (GRK2) followed by binding of beta-arrestins to the phosphorylated receptor. Binding of beta-arrestin to the receptor is a prerequisite for subsequent receptor desensitization, internalization via clathrin-coated pits, and the initiation of alternative signaling pathways. In this study we have investigated the interactions between receptors and beta-arrestin2 in living cells using fluorescence resonance energy transfer. We show that (a) the initial kinetics of beta-arrestin2 binding to the receptor is limited by the kinetics of GRK2-mediated receptor phosphorylation; (b) repeated stimulation leads to the accumulation of GRK2-phosphorylated receptor, which can bind beta-arrestin2 very rapidly; and (c) the interaction of beta-arrestin2 with the receptor depends on the activation of the receptor by agonist because agonist withdrawal leads to swift dissociation of the receptor-beta-arrestin2 complex. This fast agonist-controlled association and dissociation of beta-arrestins from prephosphorylated receptors should permit rapid control of receptor sensitivity in repeatedly stimulated cells such as neurons.