PHARMACOLOGICAL SUBSTRATES IN AGING

本项目的基本目标是研究 心血管药物药理学特性的年龄相关变化 和中枢神经系统。 虽然有丰富的文献， 年轻和年老生物体的药物反应之间的差异， 了解这些差异背后的机制。 在这 计划，我们将研究与年龄相关的药物反应性的变化， 人和实验动物模型，重点是肾上腺素能机制， 心血管和中枢神经系统。 的分子机制 对于这种变化，在受体方面，腺苷酸环化酶， 突触前功能的调节将使用人类和 动物组织 生理相关性将使用技术进行检查 电记录和刺激的方式。 脑组织移植将 可用于确定内在与外在性质的任何 与年龄相关的中枢神经系统变化。 主要的假设是 外周自主神经系统突触前和/或突触后的变化 神经效应器机制或中枢神经系统突触回路将成为 药物反应性的许多变化与衰老有关。

The basic objective of this program project is to study the mechanism of age-related changes in the pharmacological properties of the cardiovascular and central nervous systems. While there is a rich literature on differences between drug responses in young and aged organisms, little is known about the mechanisms which underlie these differences. In this program, we will study age-related changes in drug responsiveness in both man and in experimental animal models focusing on adrenergic mechanisms in the cardiovascular and central nervous systems. The molecular mechanisms for such changes, in terms of receptors, of adenylate cyclase, and of the regulation of presynaptic function will be pursued using both human and animal tissues. Physiological correlates will be examined using techniques of electrical recording and stimulation. Brain tissue transplantation will be utilized to determine the intrinsic versus extrinsic nature of any age-related central nervous changes. The major hypothesis to be pursued is that pre- and/or postsynaptic changes in the peripheral autonomic neuroeffector mechanisms or in the CNS synaptic circuitry will underlie many of the alterations in drug responsitivity seen with aging.