The purpose of the proposed research is to understand more about the function of the enteric nervous system, and particularly the way in which it controls the motility and absorptive functions of gastrointestinal tract. The experimental approach will be electrophysiological, by making intracellular recordings from neurons lying in the myenteric and submucous plexuses of the guinea-pig small intestine. Three levels of approach are planned. The first is a study of the detailed properties of the individual neurons, particularly their membrane ion channels, their cell surface receptors (particularly for catecholamines and acetylcholine), and their intracellular second messengers which couple receptors to ion channels. The second is an investigation of the way in which the nerve cells are synaptically connected; this will be done by observing the effects of surgical lesions, and by recording from pairs of neurons at the same time. The third approach is to record from single cells in circumstances in which they are more or less intact in the wall of the intestine, and responsive to the physiological synaptic inputs during reflex activity. This may allow us to construct a model for the way in which the nerve cells control peristalsis. The health related significance of this work derives from the directness of its approach to the function of gastrointestinal nerves. The enteric nervous system is involved in primary disease states, and also contributes to the pathophysiology of a wide range of conditions in which it is not primarily involved. These range from peptic ulcer to irritable bowel syndrome, from dysphagia to diabetes. The long term objective of the work is to understand the role of the enteric nervous system and the way in which it contributes to these pathological conditions.
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