MONOAMINE RECEPTOR SENSITIVITY AND MENTAL ILLNESS

我们其他调查员的工作表明贝塔和阿尔法- 血小板中肾上腺素能受体的数量和功能降低， 抑郁症患者的白细胞，提示和异常， 受体和受体后信号放大。 到 为了进一步研究这种异常的性质，我们建议研究 AC系统的受体后调节，我们将研究 β-肾上腺素能受体、G蛋白和AC系统的催化亚单位 在从患者和对照中获得的血小板和白细胞中， 用异丙肾上腺素、NaF forskolin和Mn ++刺激AC。 由于PI 系统和AC系统是负相关的，我们将研究凝血酶， NaF刺激血小板中磷酸肌醇的形成， 抑郁症患者环磷酸腺苷反应的降低伴随着 增加的PI信号系统响应。 我们的建议是基于 受体后信号调节异常假说 抑郁症的放大 我们特别假设 白细胞和血小板中G蛋白的反应性降低 抑郁症患者和AC系统的反应性下降， 伴随着PI信号系统的响应性增加。 一个 了解这种特殊的异常可能会使我们更好地了解 了解这些疾病的病理生理学。

Work done by us other investigators indicates that beta and alpha- adrenergic receptor number and function is decreased in the platelets and leukocytes of depressed patients, suggesting and abnormality in the receptor and postreceptor signal amplification in these illnesses. To further investigated the nature of this abnormality, we propose to study the postreceptor regulation of AC system, we will study the functions of beta-adrenergic receptors, G protein and catalytic subunit of the AC system in the platelets and leukocytes obtained from patients and controls by stimulating AC with isoproterenol, NaF forskolin an Mn++. Since the PI system and the AC system are inversely correlated, we will study thrombin, NaF stimulated inositol phosphate formation in platelets to examine if a decrease in cyclic AMP response in depressed patients is accompanied with an increased PI signalling system response. Our proposal is based on the hypotheses that there is a dysregulation of postreceptor signal amplification in depression. We specifically hypothesize that the responsiveness of G protein is decreased in the leukocytes and platelets of depressed patients and that a decrease in the reponsiveness of AC system is accompanied by an increased responsiveness o PI signalling system. An understanding of such specific abnormalities may lead us to a better understanding of the pathophysiology of these illnesses.