NEURAL REGULATION OF SMALL INTESTINAL MUCOSA

这是一项继续研究内在神经机制的建议。 对豚鼠肠粘膜分泌功能的影响 回肠。利用Ussing小室测定离子的研究 组织对假定的神经递质的反应将并行进行 微电极研究将确定假定的直接作用 在已识别的VIP能神经元水平上的递质。第一 具体目的是阐明VIP能运动神经元在变态反应中的作用。 电场刺激或反射激活引起的离子转运 在Ussing小室的粘膜制剂中。第二个目标是确定 通过检测刺激VIP能神经元的神经递质 Ussing小室中粘膜制剂的短路电流。第三 目的是建立可能的神经生理学作用机制。 神经递质通过检测它们对单个细胞的影响来改变运输 VIP能运动神经元。激动剂或拮抗剂将被添加到 含有完整粘膜下层的粘膜片的灌流液 神经节来表征短路电流反应的变化。这个 短路电流变化的离子基础将通过 钠和氯化物通量的放射性同位素测量的测定。 单个VIP能神经元的电和突触行为将是 通过将记录微电极直接放置到细胞体中来确定 粘膜下神经元。被刺穿的神经元将被明确地识别为 荧光黄荧光和VIP-ERGIC的存在 亲和素-生物素-过氧化物酶在同一细胞体中染色。整合了 Ussing小室研究与电生理研究 设计了粘膜下神经节细胞对可能的信使的海绵 以提供对神经生理学的更全面的见解 控制粘膜运输的机制。拟议的研究将扩大 对豚鼠体内离子转运过程的了解非常有限 控制小肠的神经生理机制 运输功能。它将提供有关神经反射的新信息。 正常情况下控制肠道内容物流动性的途径 肠道功能，或在病理生理状态期间，如 分泌性腹泻。

This is a proposal to continue investigation of intrinsic neural mechanisms that influence intestinal mucosal secretory function in the guinea pig ileum. Studies that utilize Ussing chambers to determine the ionic responses of tissues to putative neurotransmitters will be done in parallel with micorlelectrode studies that will identify direct actions of putative transmitters at the level of identified VIP-ergic neurons. The first specific aim is to clarify the role of VIP-ergic motor neurons in altered ion transport evoked by electrical field stimulation or reflex activation in mucosal preparations in Ussing chambers. The second aim will identify the neurotransmitters that excite VIP-ergic neurons by examining short-circuit current in mucosal preparations in Ussing chambers. The third aim is to establish the neurophysiological mechanisms of action of putative neurotransmitters that alter transport by examining their effects on single VIP-ergic motor neurons. Agonists or antagonists will be added to the superfusion solutions of mucosal sheets containing intact submucosal ganglia to characterize changes in short-circuit current responses. The ionic basis for changes in short-circuit current will be evaluated by determination of radioisotopic measurement of sodium and chloride fluxes. Electrical and synaptic behavior of single VIP-ergic neurons will be determined by placing recording microelectrodes directly into cell bodies of submucosal neurons. Impaled neurons will bc identified unequivocally as VIP-ergic by the presence of Lucifer Yellow fluorescence and avidin-biotin-peroxidase staining in the same cell body. Integration of the Ussing chamber studies with investigations of electrophysiological re- sponses of submucosal ganglion cells to the putative messengers is designed to provide more comprehensive insights into the neurophysiological mechanisms of control of mucosal transport. The proposed study will expand the very limited knowledge of ion transport processes in the guinea pig and of the neurophysiological mechanisms that control small intestinal transport function. It will provide new information on neural reflex pathways that govern the fluidity of the intestinal contents during normal functioning of the bowel, or during pathophysiological states such as secretory diarrhea.