MONOAMINE RECEPTOR SENSITIVITY AND MENTAL ILLNESS

这项拟议研究的长期目标是研究 情感疾病和精神分裂症病因学中的单胺受体， 并检验单胺受体敏感性的改变是否与 抗抑郁药和抗精神病药物的作用模式。在……里面 在研究单胺受体的作用时，有人提出，两种受体 这些受体的功能和数量需要在外周进行研究 取自住院精神病患者和正常人的组织 控制。有待研究的受体是肾上腺素能β受体。 人白细胞和人血小板上的α-肾上腺素能受体。这个 受体的生化功能将通过测定 激动剂促进腺苷环化酶环磷酸腺苷的产生 白细胞。脑内β-肾上腺素能受体的数量和亲和力 人类白细胞将通过结合技术进行研究，使用 肾上腺素能拮抗剂125I-氰基吲哚(CYP)。α2肾上腺素能 将通过与特定的受体结合来研究血小板中的受体 肾上腺素能激动剂，~3H-可乐定。由于一些报告显示 慢性阻塞性肺疾病患者β-肾上腺素能受体反应性降低 抑郁，这个项目将检查可能与抑郁症相关的因素 随着人类白细胞中β-肾上腺素能受体的下调。在……里面 特别是，改变儿茶酚胺水平的作用，如 检测血浆和皮质醇中的肾上腺素和去甲肾上腺素 在这些病人身上。这些研究将检验是否下调了对 β-肾上腺素能受体与情感性精神分裂症的病理生理学关系 疾病或如果它是继发性的胺水平的变化在 血浆。为了检查下调监管的地点，我们建议 研究腺苷环化酶的三个组成部分，即 受体、G蛋白和腺苷酸的调节亚单位 人类白细胞中的环化酶。为了研究血小板的作用 α2肾上腺素能受体，我们将测定密度和亲和力 用~3H-可乐定检测这些受体。由于α2肾上腺素能受体 在去甲肾上腺素释放、尿和血浆MHPG及 NE的其他代谢产物将被确定为NE周转的一个指标。 这些研究不仅有助于对生物化学的理解 精神疾病的病因学，但也有助于确定亚群的特征 因为我们知道抑郁症和精神分裂症都不是 由同质的种群组成。因此，它可能对 这些患者的诊断和治疗。

The long-term objective of the proposed study is to examine the role of monoamine receptors in the etiology of affective illness and schizophrenia, and to examine if alterations in monoamine receptor sensitivity are related to the mode of action of antidepressant and antipsychotic drugs. In examining the role of monoamine receptors, it is proposed that both the function and the number of these receptors be studied in the peripheral tissue obtained from hospitalized psychiatric patients and normal controls. The receptors to be studied are beta-adrenergic receptors in the human leukocytes and alpha-adrenergic receptors in human platelets. The biochemical function of the receptors will be studied by determining the agonist stimulated cyclic AMP production of adenylate cyclase in leukocytes. The number and the affinity of beta-adrenergic receptors in human leukocytes will be studied by binding techniques using 125I-cyanopindolol (CYP), an adrenergic antagonist. Alpha2adrenergic receptors in platelets will be studied by binding with specific alpha-adrenergic agonist, 3H-clonidine. Since some reports indicate decreased beta-adrenergic receptor responsiveness in patients with depression, this project will examine the factors which may be associated with down regulation of beta-adrenergic receptors in human leukocytes. In particular, the role of altered levels of catecholamines such as epinephrine and norepinephrine (NE) in plasma and cortisol will be examined in these patients. The studies will examine if the down regulation of beta-adrenergic receptors is related to the pathophysiology of affective illness or if it is secondary to changes in the amine levels in the plasma. In order to examine the sites of down regulation we propose to study the three components of the adenylate cyclase, that is, the receptors, the g-protein, and the regulatory subunit of the adenylate cyclase in the human leukocytes. In order to examine the role of platelet alpha2adrenergic receptor, we will determine the density and the affinity of these receptors using 3H-clonidine. Since alpha2adrenergic receptors play a role in the release of NE, urinary and plasma levels of MHPG and other metabolites of NE will be determined as an index of NE turnover. These studies may help not only in the understanding of the biochemical etiology of mental illness but will also help in characterizing subgroups of patients, since it is known that neither depression nor schizophrenia consists of a homogenous population. It may thus be beneficial in the diagnosis and treatment of these patients.