NEUROIMMUNOMODULATION PATCH CLAMP STUDIES

这项建议的长远目标是加深我们对 的细胞和亚细胞机制的基础上的过程， 神经免疫调节 越来越多的证据支持神经系统 与免疫系统相互作用。 解剖学，生化学 和生理学研究都表明了神经物质的作用， 神经肽，神经递质和激素，对几个淋巴细胞 功能协调发展的 关于这些物质调节淋巴细胞功能的方式， 基于淋巴细胞活化、有丝分裂和 容量调节依赖于离子流和神经肽， 已被证明能调节免疫反应的激素也 调节可兴奋细胞中的钾和钙通道。 因此 神经系统调节免疫的可能机制 应答是通过调节淋巴细胞离子通道和电流。 我们 因此，建议研究免疫活性的影响， 递质、肽和激素对离子通道和电流的影响 淋巴细胞。 具体目标是：1）测量，使用全细胞配置 膜片钳技术（Hamil，等，1981年，电 小鼠和人T淋巴细胞的活性，并研究 这种活动是由神经递质、神经肽和激素引起的。2)评估 不管是静止的还是增殖的T细胞， 应用神经调节剂。 3)确定第二信使系统 参与观察到的调节作用。 这些研究将为我们了解 参与淋巴细胞功能的信号转导途径， 免疫抑制剂或免疫增强剂的调节和设计 基于它们的通道阻断特性。

The long-term objective of this proposal is to further our understanding of the cellular and subcellular mechanisms underlying the process of neuroimmunomodulation. Evidence has accumulated to support the idea that the nervous system interacts with the immune system. Results from anatomical, biochemical and physiological studies all suggest an effect of neural substance, neuropeptides, neurotransmitters and hormones, on several lymphocyte functions. An idea of the way these substances can modulate lymphocyte function is based on the observation that lymphocyte activation, mitogenesis and volume regulation are dependent on ionic fluxes, and neuropeptides and hormones that have been shown to modulate the immune response also modulate potassium and calcium channels in excitable cells. Thus, a possible mechanism by which the nervous system regulates the immune response is by modulating lymphocyte ion channels and currents. We therefore propose to study the effects of immunologically active transmitters, peptides and hormones on the ionic channels and currents of lymphocytes. The specific aims are: 1) Measure, using the whole cell configuration of the patch clamp technique (Hamil, et al., 1981), the electrical activity of murine and human T lymphocytes and study the modulation of this activity by neurotransmitters, neuropeptides and hormones. 2) Assess whether resting or proliferating T cells are more responsive to the applied neuromodulators. 3) Determine the second messenger system involved in the modulatory effect(s) observed. These studies will provide relevant information for our understanding of the signal transduction pathways involved in lymphocyte function and regulation and the design of immunosuppressive or immunoenhancing agents on the basis of their channel blocking properties.