RECEPTOR PHARMACOLOGY IN ATOPIC DERMATITIS

特应性皮炎是一种皮肤炎，通常 发生于有一种或多种特应性的个人或家族病史的人 疾病(如哮喘、过敏性鼻炎或特应性皮炎)。每一个 这些情况可能显示免疫学和药理学的证据。 功能障碍，但这种异常往往在主题中最明显 皮炎。这个项目的重点是免疫学的分子基础。 和药物的相互作用。 这些研究利用了单核白细胞，它表现出许多 特应性皮炎的免疫异常。我们的研究还包括 患者存在环核苷酸代谢异常 细胞。环磷酸腺苷二酯酶活性升高，膜 特应性白细胞中的β-肾上腺素受体结合改变。类似 低氧暴露对正常单核白细胞的影响 组胺浓度。这些变化似乎很可能有一个 共同的起源和确定基本的分子改变位置可能 有助于了解特应性疾病的发病机制。 组胺引起单核白细胞的变化，并提供一种有用的 用于描绘特应症分子缺陷和澄清分子缺陷的探针 炎性介质对免疫相关细胞的影响。这个 组胺对受体结合、腺苷环化酶活性的影响 将测定蛋白激酶活性和环磷酸腺苷周转率，从而 对周期中的各个步骤进行全面评估 核苷酸途径。与患者单核白细胞的比较 特应性皮炎将在每一步进行确认，以确认其有效性 组胺模型。此外，百日咳毒素，最近显示出 作用于腺苷环化酶调节单位的特定亚基，将是 评估与组胺诱导和特应性细胞的相似性 异常现象。这种毒素很早就知道会导致特应性。 动物的特性。 上述研究涉及腺苷环化酶连接的受体系统。 此外，最近的研究表明，第二类主要的受体与 肌醇磷脂代谢。初步证据表明 特应性和组胺治疗的正常人群中这一通路的参与 单核白细胞。肌醇磷脂的进一步研究 新陈代谢将允许评估异常和关系 1异位性皮炎的环核苷酸系统。

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.