ADRENERGIC CONTROL OF ADENYLATE CYCLASE IN AGING

衰老通常与肾上腺素能反应性的改变有关。 许多 的肾上腺素能反应主要是通过调节 腺苷酸环化酶的活性。 β受体 受体介导腺苷酸环化酶的刺激，而 α 2肾上腺素能受体抑制酶。 β-肾上腺素能介导 通常观察到腺苷酸环化酶活性的刺激 老年下降，而α 2-肾上腺素能调节腺苷酸环化酶 还没有被作为老化的函数来研究。 进一步认识到 参与刺激和抑制的分子事件 腺苷酸环化酶现在允许详细检查， 肾上腺素能刺激转导中各个步骤的改变， 与衰老有关的疾病 本项目建议审查 β-肾上腺素能刺激心肌腺苷酸环化酶活性 青年和老年大鼠的多形核白细胞和青年和老年大鼠的多形核白细胞 老年人，在激素之间的耦合效率方面， 受体、刺激性鸟嘌呤核苷酸调节蛋白和催化 单位 α 2肾上腺素能抑制腺苷酸环化酶的作用 还将检查年轻人和老年人受试者的血小板， 确定是否有任何改变之间的耦合， α-肾上腺素能受体，抑制性GTP调节蛋白， 催化单元作为老化的函数。 还将建立条件 这将允许检查β-和α 2-肾上腺素能 大鼠小脑腺苷酸环化酶活性的调节 海马区。 然后将这些属性在年轻的 老年老鼠 还将尝试溶解GTP调节酶。 蛋白质和小脑环化酶的催化单位，以确定 这些成分的变化是否独立于 膜的一般性质的改变。 这些研究 应该提供第一次详细检查与年龄有关的变化， 腺苷酸环化酶的肾上腺素能调节， 参与刺激和抑制活动的步骤，并将 允许推测是否生理变化， 与衰老相关的肾上腺素能反应可能是由 腺苷酸环化酶调节改变。

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.