PHARMACOLOGICAL SUBSTRATES IN AGING

本项目的基本目标是研究黄曲霉毒素的作用机制。 心脑血管药理特性的增龄变化 和中枢神经系统。虽然有丰富的文献关于 年轻生物体和老年生物体的药物反应差异很小 了解这些差异背后的机制。在这 计划，我们将研究年龄相关的药物反应性的变化在两个 在关注肾上腺素能机制的人和实验动物模型中 心血管和中枢神经系统。分子机制 对于这些变化，在受体方面，腺苷环化酶，以及 突触前功能的调节将使用人类和 动物组织。生理学的相关性将使用技术进行检验 电记录和刺激。脑组织移植将 被用来确定任何 与年龄相关的中枢神经改变。要追寻的主要假设是 突触前和/或突触后外周自主神经的变化 神经效应机制或在中枢神经系统突触回路中将是基础 药物反应性的许多变化都是随着年龄的增长而出现的。

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.