ATRIAL NATRIURETIC PEPTIDE AND ALDOSTERONE SECRETION

拟议的研究的主要目的是定义细胞 和心钠素的分子机制 心钠素(ANP)抑制荷尔蒙刺激的肾上腺皮质激素分泌 肾上腺小球细胞。ANP，通过一个明显的表面 受体可抑制大鼠肾上腺素分泌 血管紧张素II、细胞外钾与促肾上腺皮质激素 激素(ACTH)。其中每一项的刺激作用 激动剂是通过激活细胞蛋白激酶来调节的。 使用新分离的小牛肾上腺细胞，我们将 确定： 1)如果ANP改变细胞稳态浓度 环核苷酸(增加cGMP，降低cAMP)和/或 改变环核苷酸周转的状态。 2)如果这些信号的心钠素作用，调制受体连锁 AII、ACTH、钾引发的信号转导事件。 3)如果ANP阻止细胞蛋白激酶的激活或 增强细胞磷蛋白的刺激作用 磷酸酶。这些研究将详细说明生物化学 ANP在肾上腺细胞中的作用机制，因此，将 有助于实现心钠素作为一种药物的潜力 盐、水代谢紊乱的处理与治疗 高血压。

The major aim of the proposed research is to define the cellular and molecular mechanism by which atrial natriuretic peptide (ANP) inhibits hormone stimulated aldosterone production from the adrenal glomerulosa cell. ANP, via a distinct surface receptor, inhibits the rate of aldosterone secretion stimulated by angiotensin II, extracellular potassium and adrenocorticotrophic hormone (ACTH). The stimulatory action of each of these agonists is mediated by the activation of cellular protein kinases. Using freshly isolated cells from calf adrenals, we will determine: 1) If ANP changes the cellular steady state concentration of cyclic nucleotides (increasing cGMP, decreasing cAMP) and/or alters the state of cyclic nucleotide turnover. 2) If these signals of ANP action, modulate receptor linked signal transduction events initiated by AII, ACTH, potassium. 3) If ANP prevents the activation of cellular protein kinases or enhances the stimulation of cellular phosphoprotein phosphatases. These studies will detail the biochemical mechanism of ANP action in the adrenal cell and as such, will help to realize the potential of ANP as a drug to be used in managing disorders of salt and water metabolism and in treating hypertension.