ANGIOTENSINS PROSTAGLANDINS--ANDRENERGIC INTERACTIONS

我们建议研究肾上腺素能 神经递质、去甲肾上腺素和血管紧张素II(AII)刺激 前列腺素(PG)合成及其对肾上腺素能的影响 神经效应器事件与血管紧张素转换酶的代谢作用 心血管系统中的儿茶酚胺。我们将解决 以下主题：1.肾上腺素能的类型的特征 参与儿茶酚胺对PG作用的受体(S) 部分心脏(室肌细胞和冠脉)的合成 微血管内皮细胞)和肾脏(肾小球、系膜和肾小球 肾髓质间质)细胞。2.营队的贡献及 蛋白激酶C的激活对儿茶酚胺对PG的作用 在完整的心脏和肾脏以及细胞培养中的合成，利用 这些第二信使的选择性激活物和抑制物 系统。3.花生四烯酸(AA)来源的测定 从组织脂质中释放PG合成以响应 神经激素刺激。组织脂质将被单独标记 含有各种放射性磷脂和甘油三酯 和产生放射性标记的产品，包括PG，在 接下来将观察对神经激素刺激的反应。4.调制 通过PGs对心脏中儿茶酚胺的脂解作用 通过测定外源PGs、AA和 PG合成的抑制剂。最后，我们将调查 AA产物影响药物释放的机制 肾上腺素能神经递质及其交感后作用 去甲肾上腺素。我们将对单个PG使用RIA和 薄层、高效液相和液体闪烁计数法测定 标记甘油脂和儿茶酚胺代谢产物。 这些研究将进一步加深我们对心力衰竭发病机制的理解。 心血管调节中的神经激素相互作用 在健康和疾病中发挥作用。

We propose to investigate the mechanism by which adrenergic neurotransmitter, norepinephrine and angiotensin II (AII) stimulate prostaglandin (PG) synthesis and PGs influence adrenergic neuroeffector events and the metabolic actions (lipolysis) of catecholamines in the cardiovascular system. We will address the following topics: 1. characterization of the type of adrenergic receptor(s) involved in the action of catecholamines on PG synthesis in selected cardiac (ventricular myocytes and coronary microvascular endothelial) and renal (glomerular messangial and renomedullary interstitial) cells. 2. Contribution of cAMP and protein kinase C activation to the action of catecholamines on PG synthesis in intact heart and kidney and in cell cultures, utilizing selective activators and inhibitors of these second messenger systems. 3. Determination of the source of arachidonic acid (AA) for PG synthesis released from tissue lipids in response to neurohormonal stimuli. Tissue lipids will be individually labeled with various classes of radioactive phospholipids and triglycerides and generation of radiolabeled products, including PGs, in response to neurohormonal stimuli will be followed. 4. Modulation by PGs of the lipolytic action of catecholamines in the heart will be assessed by determining the effect of exogenous PGs, AA, and inhibitors of PG synthesis. Finally, we will investigate the mechanism by which products of AA influence release of the adrenergic neurotransmitter as well as the postjunctional actions of norepinephrine. We will utilize RIAs for individual PGs and TLC and HPLC and liquid scintillation counting for determination of products of labeled glycerolipid and catecholamine metabolism. These studies will further our understanding of the mechanisms of neurohormonal interactions in the regulation of cardiovascular function in health and disease.