RECEPTOR PHARMACOLOGY IN ATOPIC DERMATITIS

特应性皮炎是一种皮肤炎症性疾病， 发生在具有一种或多种特应性疾病的个人或家族史的人中。 疾病（即，哮喘、过敏性鼻炎或特应性皮炎）。 中的每 这些情况可能显示出免疫和药理学的证据， 功能障碍，但这种异常往往是最明显的主题 皮炎 该项目的重点是免疫学的分子基础， 和药理学相互作用。 这些研究利用了单核白细胞，其表现出许多 特应性皮炎的免疫异常 我们的研究也 证实了患者的环核苷酸代谢异常， 细胞 环腺苷酸磷酸二酯酶活性升高， β-肾上腺素能受体结合在特应性白细胞中改变。 类似 正常单核白细胞暴露于低浓度的 组胺的浓度。 这些变化似乎有一个 共同的起源和确定改变的基本分子位点可以 从而理解特应性疾病的病理机制。 组胺引起单核白细胞的变化， 用于描绘特应性中的分子缺陷和用于澄清 炎症介质对免疫相关细胞的影响。 的 组胺对受体结合，腺苷酸环化酶活性， 将测定蛋白激酶活性和环AMP周转率，从而 提供循环中各个步骤的综合评估 核苷酸途径 与患者单核白细胞的比较 将在每一步进行特应性皮炎的检查，以确认 组胺模型。 此外，百日咳毒素，最近显示， 作用于腺苷酸环化酶调节单元的特定亚基，将是 评价了与组胺诱导和特应性细胞 异常 这种毒素很久以前就被认为会引起特应性 动物的性格。 上述研究涉及腺苷酸环化酶连接的受体系统。 此外，最近的研究表明，第二大类受体与 肌醇磷脂代谢。 初步证据显示 这一通路参与特应性和组胺治疗的正常 单核白细胞 肌醇磷脂的进一步研究 代谢将允许评估异常和关系 环核苷酸系统在特应性皮炎中的作用。

Atopic dermatitis is a cutaneous inflammatory condition which usually occurs in persons with a personal or family history of one or more atopic diseases (i.e., asthma, allergic rhinitis or atopic dermatitis). Each of these conditions may show evidence of immunologic and pharmacologic dysfunction, but such aberrancies tend to be most pronounced in topic dermatitis. This project is focused on the molecular basis of immunologic and pharmacologic interactions. These studies have utilized mononuclear leukocytes which manifest a number of immunologic abnormalities in atopic dermatitis. Our studies have also demonstrated abormalities of cyclic nucleotide metabolism in patients' cells. Cyclic AMP-phosphodiesterase activity is elevated and membrane beta-adrenegic receptor binding is altered in atopic leukocytes. Similar changes are induced in normal mononuclear leukocytes exposed to low concentrations of histamine. It seems probable that these changes have a common origin and identifying the basic molecular site of alteration may lead to an understanding of pathomechanisms in atopic disease. Histamine causes changes in mononuclear leukocytes and provides a useful probe for delineating molecular defects in atopy and for clarifying the effects of the inflammatory mediator on immune-associated cells. The action of histamine on receptor binding, adenylate cyclase activity, protein kinase activity and cyclic AMP turnover will be determined, thus providing comprehensive assessment of various steps in the cyclic nucleotide pathway. Comparisons with mononuclear leukocytes of patients with atopic dermatitis will be made at each step to confirm the usefulness of the histamine model. In addition, pertussis toxin, recently shown to act on a specific subunit of the adenylate cyclase regulatory unit, will be evaluated for similarities to hisatmine-induced and atopic cellular abnormalities. This toxin has long been known to induce atopic characeristics in animals. The above studies relate to the adenylate cyclase linked receptor system. In addition, recent studies show a second major class of receptors linked to inositol phospholipid metabolism. Preliminary evidence indicates involvement of this pathway in atopic and histamine-treated normal mononuclear leukoycytes. Further investigations of inositol phospholipid metabolism will allow evaluation of abnormalities and relationships with1the cyclic nucleotide system in atopic dermatitis.