ELECTRICAL AND NEURAL CONTROL OF PYLORIC MOTILITY

实验拟研究的基本电生理和 胃十二指肠连接处的神经调节。 的这个区域 胃肠道，包括远端胃窦、幽门 括约肌和近端十二指肠，被认为是重要的， 控制胃内容物被排空到胃中的速率， 小肠 它的生理学是复杂的， 描述了以前的细胞外电记录和整个- 动物研究。 幽门肌层的横截面条带， 已经开发出分离的平滑肌细胞， 研究神经递质作用的离子机制。 表征由幽门表达的离子电导的实验 肌肉细胞将决定异质性的原因， 通过大脑不同深度记录的电活动 肌层 使用完整的肌肉，胆碱能，非- 肾上腺素能-非胆碱能（NANC）和非胆碱能兴奋性 将表征神经的电和机械活动。 在描述了假定的神经递质对 完整的肌肉，膜片钳研究将进行研究， 由每种试剂激活的特定电导。 初步证据 表明胆碱能和非胆碱能兴奋性递质 通过激活非选择性阳离子传导起作用， 而NANC发射器激活钾电导。 这些研究 将特别有用，因为它们将揭示特定的离子 这些通道蛋白可以作为开发 控制异常幽门括约肌功能的治疗剂。 还将进行研究，以确定调节 神经递质的释放 最近的研究表明， 氧化物可以介导一部分的NANC神经传递， 胃十二指肠连接处 形态学研究将调查 由表达一氧化氮合酶的神经支配，和 实验将试图确定第二信使系统 由一氧化氮刺激激活 生物化学研究将 测量一氧化氮的释放及其对循环的影响， 核苷酸水平。 这些研究使用了多种技术， 将提供基本的电气和神经控制的概述 调节胃十二指肠连接部运动的机制 这可能有助于解释幽门在调节胃运动中的作用， 清空

Experiments are proposed to study the basic electrophysiological and neural regulation of the gastroduodenal junction. This region of the gastrointestinal tract, which includes the distal antrum, pyloric sphincter, and proximal duodenum, is thought to be important in controlling the rate at which gastric contents are emptied into the small intestine. Its physiology is complicated and has not been fully described by previous extracellular electrical recordings and whole- animal studies. Cross-sectional strips of the pyloric muscularis and isolated smooth muscle cells have been developed to allow precise studies of the ionic mechanisms of the effects of neurotransmitters. Experiments characterizing the ionic conductances expressed by pyloric muscle cells will determine the reasons for the heterogeneity in the electrical activity recorded at different depths through the muscularis. Using intact muscles, the effects of cholinergic, non- adrenergic-non-cholinergic (NANC), and non-cholinergic excitatory nerves on electrical and mechanical activities will be characterized. After characterizing the effects of putative neurotransmitters on intact muscles, patch clamp studies will be performed to study the specific conductances activated by each agent. Preliminary evidence suggests that cholinergic and non-cholinergic excitatory transmitters function via the activation of a non-selective cation conductance, while NANC transmitters activate potassium conductances. These studies will be particularly useful because they will reveal specific ion channel proteins that could be targeted in attempts to develop therapeutic agents to control abnormal pyloric sphincter function. Studies will also be performed to determine the factors that regulate the release of neurotransmitters. Recent work has shown that nitric oxide may mediate a portion of the NANC neurotransmission in the gastroduodenal junction. Morphological studies will investigate the innervation by nerves that express nitric oxide synthase, and experiments will attempt to determine the 2nd messenger systems activated by nitric oxide stimulation. Biochemical studies will measure nitric oxide release and the effects of this on cyclic nucleotide levels. These studies, using a variety of technologies, will provide an overview of the basic electrical and neural control mechanisms that regulate the motility of the gastroduodenal junction and may help to explain the role of the pylorus in regulating gastric emptying.