ANGIOTENSINS PROSTAGLANDINS--ANDRENERGIC INTERACTIONS

我们建议研究肾上腺素能神经元 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）的合成和PG影响肾上腺素能 神经效应事件和代谢作用（脂肪分解） 心血管系统中的儿茶酚胺。 我们将解决 以下主题：1.肾上腺素能神经元类型的表征 参与儿茶酚胺对PG作用的受体 在选定的心脏（心室肌细胞和冠状动脉）中的合成 微血管内皮）和肾脏（肾小球系膜和 肾髓质间质）细胞。 2. cAMP和 蛋白激酶C激活对儿茶酚胺对PG的作用 在完整的心脏和肾脏中以及在细胞培养物中的合成，利用 这些第二信使的选择性激活剂和抑制剂 系统. 3.花生四烯酸（AA）来源的确定 对于组织脂质释放的PG合成， 神经激素刺激 将单独标记组织脂质 含有各种放射性磷脂和甘油三酯 以及放射性标记产物（包括PG）的产生， 将跟踪对神经激素刺激的反应。 4.调制 通过前列腺素的脂肪分解作用的儿茶酚胺在心脏将 通过测定外源性PG、AA和 PG合成的抑制剂。 最后，我们将调查 AA产品影响释放的机制 肾上腺素能神经递质以及连接后作用 去甲肾上腺素 我们将利用RIA为个人PG和 薄层色谱法、高效液相色谱法和液体闪烁计数法测定 标记的甘油脂质和儿茶酚胺代谢产物。 这些研究将进一步加深我们对 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.