REGULATION OF IMIDAZOLINE BINDING SITES IN DEPRESSION

在他的第一个奖项，博士Piletz（PI）。和同事们获得了 证据表明，非肾上腺素能，咪唑啉选择性受体可能与 抑郁症 他们发现，单相抑郁症患者表现出一种 p-125 IC的结合密度（Bmax）显著升高（p=.002） 与健康对照组相比， 或广泛性焦虑症患者。 血小板血浆网站 膜与脑中的咪唑啉-1受体（I1 R）几乎相同 茎基于其对多种化合物的亲和力。 血小板p125 IC 抗抑郁药物治疗后患者的结合率下降。 此外，类似物p-NH 4 - 3 H-clonidine的结合， 显著升高，在黄体晚期的妇女与烦躁不安 经前变化（PMS），但不是在正常月经周期的妇女。 在这个应用程序中，Piletz博士与I1 R的发现者（Dr. Ernsberger）研究I1结合调节的分子基础 网站. 将使用人巨核细胞肿瘤细胞系（MEG-01）作为肿瘤细胞系。 血小板受体模型。 Piletz博士展示了这种独特的细胞系 拥有I1位点，并且实际上可以产生血小板样颗粒， 文化 利用Piletz博士在cDNA方面的博士后经验， 一组克隆了类似受体的同事， 建议在MEG-01细胞中克隆I1受体cDNA。 这些研究将 回答有关血小板I1位点的基本问题， 健康与疾病及其作为抑郁症标志物可能效用 疾病和PMS。

During his FIRST award, Dr. Piletz (the P.I.) and colleagues obtained evidence that non-adrenergic, imidazoline-selective receptors may be linked to depression. They found that unipolar depressed patients displayed a significant elevation (p=.002) in the binding density (Bmax) of p-125 IC) to an imidazoline-selective site on platelets, compared to healthy controls or patients with generalized anxiety disorder. The site on platelet plasma membranes was nearly identical to the Imidazoline-1 Receptor (I1R) in brain stem based on its affinity for a variety of compounds. Platelet p125 IC binding declined in patients following antidepressant drug treatment. Additionally, the binding of an analogue, p-NH4-3H-clonidine, was significantly elevated in the late luteal phase of women with dysphoric premenstrual changes (PMS), but not in women with normal menstrual cycles. In this application Dr. Piletz teams up with the discoverer of the I1R (Dr. Ernsberger) to investigate the molecular basis of regulation of I1 binding sites. A human megakaryocytic tumor cell line (MEG-01) will be used as a model of platelet receptors. This unique cell line was shown by Dr. Piletz to possess I1 sites, and can actually produce platelet-like particles in culture. Drawing on Dr. Piletz's postdoctoral experience with cDNA, and on a team of colleagues who have cloned similar receptors, this application proposes to clone the I1 receptor cDNA in MEG-01 cells. These studies will answer fundamental questions about the platelet I1 site, its regulation in health and disease and its possible utility as a marker in depressive illness and PMS.