ADRENERGIC CONTROL OF ADENYLATE CYCLASE IN AGING

衰老通常与肾上腺素能反应性改变有关。许多 肾上腺素能反应主要是通过调节 质膜中腺苷环化酶的活性。β-肾上腺素能 受体介导腺苷酸环化酶的刺激，而 α2-肾上腺素能受体抑制这种酶。β-肾上腺素能介导 腺苷环化酶活性的刺激通常被观察到是 老年衰退，而α2-肾上腺素能调节腺苷环化酶 没有被作为衰老的函数进行检查。不断提高对 参与刺激和抑制的分子事件 腺苷环化酶现在允许对可能的 肾上腺素能刺激转导的不同步骤的变化， 它们与衰老有关。本项目建议审查 β-肾上腺素能刺激心肌腺苷环化酶活性 幼年和老年大鼠的中性粒细胞和幼年和老年大鼠的中性粒细胞 老年人，在荷尔蒙偶联效率方面 受体、刺激性鸟核苷酸调节蛋白和催化 单位。α2-肾上腺素能抑制血管内皮细胞腺苷环化酶 年轻和老年人类受试者的血小板也将被检查 确定之间的耦合是否有任何变化 α-肾上腺素能受体，抑制性GTP调节蛋白和 催化单元作为老化的函数。还将建立条件 这将允许同时检查β-和α2-肾上腺素能 大鼠小脑和脑内腺苷环化酶活性的调节 分别为海马体。然后，这些特性将被用来比较年轻的 和衰老的老鼠。还将尝试解决GTP监管问题 蛋白质和小脑环化酶催化单位的测定 这些组件中是否发生独立于 膜的一般性质的改变。这些研究 应提供对年龄相关变化的第一个详细检查 腺苷环化酶对肾上腺素能的调节作用 刺激和抑制活动的步骤，以及意志 允许人们推测生理上的变化是否 与衰老相关的肾上腺素能反应可能由以下因素解释 腺苷环化酶调节的改变。

Aging is generally associated with altered adrenergic responsiveness. Many of the adrenergic responses are mediated primarily through the regulation of adenylate cyclase activity in the plasma membrane. Beta-adrenergic receptors mediate the stimulation of adenylate cyclase, whereas Alpha2-adrenergic receptors inhibit the enzyme. Beta-adrenergic mediated stimulation of adenylate cyclase activity has generally been observed to decline in old age, while Alpha2-adrenergic regulation of adenylate cyclase has not been examined as a function of aging. Increasing awareness of the molecular events involved in both the stimulation and inhibition of adenylate cyclase now allows a detailed examination to be made of possible alterations in various steps in the transduction of adrenergic stimuli, which are associated with aging. The present project proposes to examine the Beta-adrenergic stimulated adenylate cyclase activity of the myocardium of young and aged rats and the polymorphonuclear leukocytes of young and old humans, in terms of the efficiency of coupling between hormone receptors, stimulatory guanine nucleotide regulatory protein and catalytic unit. The Alpha2-adrenergic inhibition of adenylate cyclase of the platelets of young and old human subjects will also be examined to determine whether there is any alteration in the coupling between the Alpha-adrenergic receptor, the inhibitory GTP regulatory protein and catalytic unit as a function of aging. Conditions will also be established which will allow the examination of the both Beta- and Alpha2-adrenergic regulation of the adenylate cyclase activity in rat cerebellum and hippocampus, respectively. These properties will then be compared in young and aged rats. Attempts will also be made to solubilize the GTP regulatory protein and catalytic unit of cerebellar cyclase in order to determine whether changes in these components occur which are independent of alterations in the general properties of the membrane. These studies should provide the first detailed examination of age-related changes in the adrenergic regulation of adenylate cyclase in terms of each of the coupling steps involved both in stimulation and inhibition of activity, and will allow speculations to be made as to whether the physiological changes in adrenergic responses associated with senescence might be accounted for by altered adenylate cyclase regulation.