ADENOSINE DERIVATIVES AND TRANSMITTER RELEASE

腺苷衍生物和递质释放

• 批准号: 3394981
• 负责人: EUGENE M SILINSKY
• 金额: $ 16.3万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-05-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3394981
• 关键词: Anura; acetylcholine; adenosine triphosphate; calcium channel; cations; electrophysiology; fresh water environment; inhibitor /antagonist; laboratory rat; liposomes; membrane potentials; motor neurons; myenteric plexus; nerve endings; neural plasticity; neurochemistry; neuromuscular transmission; neuropharmacology; neurotransmitter metabolism; peripheral nervous system; preganglionic fiber; receptor; second messengers

The overall objective of this research,is to further our knowledge of the mechanisms of transmitter release and its modulation by adenosine derivatives. For this next period of support,it is intended to use electrophysiological,luminometric and liposome-based methods to study the following four aspects of purinergic transmission in the vertebrate peripheral nervous system:1) We will study further how adenosine receptor activation is transduced into the inhibition of acetylcholine (ACh) secretion at motor nerve endings. Does adenosine inhibit ACh release by reducing Ca entry through voltage-gated membrane channels or impair the intracellular actions of Ca? 2) We will study the effects of adenosine in stimulating quantal transmitter release. Both the receptors responsible for increasing transmitter release and the mechanisms underlying the stimulatory effect of adenosine will be studied at mammalian motor nerve terminals and at nerve endings in submucous plexus of the mammalian enteric nervous system. 3) We will investigate the possibility that ATP may be an excitatory neurotransmitter in the submucous plexus. Both the postsynaptic effects of ATP derivatives and the calcium-dependent release of ATP will be studied. 4) We will investigate the possibility that adenosine is a modulator of peripheral synaptic plasticity reflected as long-term potentiation in frog sympathetic chain ganglia. Adenosine and its congeners,by their actions on synaptic junctions,have been implicated as natural mediators of a number of physiological, behavioral and pathological processes. Studying the mechanisms by which adenosine exerts its physiological effects at sites in the vertebrate nervous system that allow accurate electrophysiological measurements of secretions is likely to provide useful basic information on the underlying mechanisms by which purines regulate neuronal behavior.

这项研究的总体目标是加深我们对 递质释放机制及腺苷的调节作用 衍生品。在下一阶段的支持中，它打算使用 电生理、发光学和脂质体为基础的方法研究 脊椎动物体内嘌呤能传递的以下四个方面 周围神经系统：1)我们将进一步研究腺苷受体如何 激活转化为乙酰胆碱(ACh)的抑制 运动神经末梢的分泌物。腺苷是否通过抑制ACh的释放 减少通过电压门控膜通道的钙内流或损害 钙离子在细胞内的作用我们将研究腺苷对 刺激量子发射器的释放。两个受体都负责 用于增加发射器的释放和潜在的机制 将研究腺苷对哺乳动物运动神经的刺激作用 哺乳动物粘膜下神经丛的终末和神经末梢 肠道神经系统。3)我们将调查ATP是否可能 可能是粘膜下神经丛中的兴奋性神经递质。这两个 三磷酸腺苷衍生物的突触后效应与钙依赖性释放 将对ATP进行研究。4)我们将调查以下可能性： 腺苷是外周突触可塑性的调节器，反映为 蛙交感神经链神经节的长时程增强。 腺苷及其同系物，通过它们对突触连接的作用， 被牵连为许多生理， 行为和病理过程。研究其作用机制。 腺苷在脊椎动物的某些部位发挥其生理作用 神经系统，允许准确的电生理测量 分泌物很可能提供有关潜在疾病的有用基本信息 嘌呤调节神经元行为的机制。