The objectives of this research are to investigate the physiological role of neuro-transmitter co-localization and release in the mammalian sympathetic nervous system and to understand the relationship between these transmitters and the maintenance of visceral homeostasis. The results of this study will expand our understanding of the integrative capacity of synaptic interactions between elements that posses a number of transmitters that may be released under different of activity. Understanding the cellular mechanism of ganglionic neurotransmission and the sympathetic innervation of end-organs is essential to the design of therapies for the treatment of gastrointestinal and vascular disorders. The experiments described here are designed to identify the chemical substances that are used by these sympathetic neurons as neurotransmitters and to understand their mechanism of action. Using dissociated cell culture, it will be possible to study the synaptic interactions between neurons and between neurons and other target cells in a greatly simplified situation. In the extreme condition, it will be possible to study a single neuron grown in isolation. Although the synaptic interactions may still be complex, the number of interacting elements can be controlled. The expression of neurotransmitters will be assayed using a combination of electrophysiological, cytochemical, and biochemical techniques. The physiological effects of these transmitters will be examined by observing their effects when applied directly and by observing synaptically transmitted effects. The use of pharmacological antagonists will help to identify the transmitters being released. the results obtained in this study will promote investigations of cellular function in intact ganglia. A final objective of this study is to understand the mechanism that regulate the expression of the transmitters. This objective arises from the observation that in vivo there are specific patterns in the distribution of co- localized transmitters. The possibility that neurons may be induced to express specific arrays of transmitters by their targets will be investigated.
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