ROLE OF ADENOSINE AND STEROIDS IN MAST CELL BIOCHEMISTRY

腺苷是一种有效的内源性冠状血管舒张介质， 血小板聚集抑制和类固醇生成，其水平增加 在体内和面对肺缺氧或抗原攻击时， 在体外用几种促分泌素刺激肥大细胞后。 它 也显示出增强抗原刺激的大鼠血清肥大细胞 通过作用于细胞表面腺苷受体释放介质。 皮质类固醇是有效的抗炎激素， 肾上腺皮质抑制慢性炎症后肥大细胞介质释放 体内给药。 探讨在临床应用中， 腺苷和类固醇在肥大细胞分泌过程中的作用， 比较和对比肥大细胞介质增强剂和抑制剂 大鼠血清素和小鼠骨的释放、功能和药理学研究 骨髓肥大细胞将在这些试剂存在下进行。 将评估腺苷释放和细胞ATP含量的波动 通过HPLC测定肥大细胞的上清液和沉淀， 茶碱地塞米松和克罗酚钠 肥大细胞腺苷 受体将通过利用放射性配体结合直接表征 (3H)腺苷或更特异性的标记的腺苷激动剂， 对腺苷脱氨酶有抵抗力。 潜在生化改变 由腺苷及其类似物诱导的如磷脂的变化， 环AMP和花生四烯酸代谢，以及磷脂酶A2 以及C和蛋白激酶活性。 解离 脱颗粒与白三烯和白藜芦醇生成之间的关系 将通过仔细比较这两种调解人的途径来探讨 花生四烯酸代谢物的释放和精确定量。 皮质类固醇诱导脂调节蛋白（一种磷脂酶）的产生 抑制蛋白 肥大细胞磷脂酶A2和C活性 在长期类固醇给药后和磷脂周转的变化 并评估二酰基甘油水平。 确定具体步骤 皮质类固醇对肥大细胞分泌的影响将是 尝试通过添加外源花生四烯酸代谢产物和融合剂 磷脂酶产物来逆转介质释放的抑制。 一 进一步了解腺苷和类固醇的生物化学， 与肥大细胞介质释放相关的药物可能有助于药物的开发 可用于治疗哮喘和过敏。

Adenosine is a potent endogenous mediator of coronary vasodilation, platelet aggregation inhibition, and steroidogenesis, whose levels increase markedly in vivo and in the face of pulmonary hypoxia or antigen challenge and in vitro after mast cell stimulation with several secretagogues. It has also been shown to potentiate antigen-stimulated rat serosal mast cell mediator release by its action on cell surface adenosine receptors. Corticosteroids are effective anti-inflammatory hormones produced by the adrenal cortex that inhibit mast cell mediator release after chronic in vivo administration. To explore the importance and the mechanisms of action of adenosine and steroids in the mast cell secretory process and to compare and contrast a potentiator and an inhibitor of mast cell mediator release, functional and pharmacologic studies of rat serosal and mouse bone marrow mast cells will be conducted in the presence of these agents. Adenosine release and fluctuations in cellular ATP content will be assessed by HPLC of supernatants and pellets from mast cells grown in the presence of theophylline, dexamethasone, and sodium cromolyn. Mast cell adenosine receptors will be directly characterized by radioligand binding utilizing (3H) adenosine or a more specific labeled adenosine agonist that is resistant to adenosine deaminase. Potential biochemical alterations induced by adenosine and its analogs such as changes in phospholipid, cyclic AMP, and arachidonic acid metabolism, as well as phospholipase A2 and C and protein kinase activities, will be studied. The dissociation between degranulation and generation of leukotrienes and prostaglandins will be explored by a careful comparison of these two avenues of mediator release and a precise quantitation of arachidonic acid metabolites. Corticosteroids induce the production of lipomodulin, a phospholipase inhibitory protein. The activities of mast cell phospholipases A2 and C after chronic steroid administration and changes in phospholipid turnover and diacylglycerol levels will be assessed. Identifying the specific step where corticosteroids exert their effect on mast cell secretion will be attempted by adding exogenous arachidonic acid metabolites and fusogenic phospholipase products to reverse the inhibition of mediator release. A further understanding of the biochemistry of adenosine and steroids as they relate to mast cell mediator release may aid in the development of agents useful in the treatment of asthma and allergy.