Hansen M B
Department of Surgical Gastroenterology K, Bispebjerg University Hospital of Copenhagen, NV, Denmark.
Physiol Res. 2003;52(1):1-30.
Neurohumoral substances and their receptors play a major part in the complex regulation of gastrointestinal motility and have therefore been the predominant targets for drug development. The numerous receptors involved in motility are located mainly on smooth muscle cells and neuronal structures in the extrinsic and intrinsic parts of the enteric nervous system. Within this system, receptor agonists and antagonists interacts directly to modify excitatory or inhibitory signals. In view of this complexity it is not surprising that our knowledge about the mechanisms of actions of the various neurohormones and drugs affecting gut motility has been rather fragmented and incomplete. However, recently substantial progress has been achieved, and drug therapy for gut dysmotility is emerging, based primarily on neurohumoral receptors. This paper presents a selective review of the neurohumoral regulatory mechanisms of gastrointestinal motility. In this context, the physiology and pharmacology of the smooth muscle cells, gastrointestinal motility and dysmotility, the enteric nervous system, gastrointestinal reflexes, and serotonin is presented. Further investigation and understanding of the transmitters and receptors involved in especially the reflex activation of peristalsis is crucial for the development of novel therapies for motility disorders.
神经体液物质及其受体在胃肠运动的复杂调节中起主要作用,因此一直是药物研发的主要靶点。参与胃肠运动的众多受体主要位于肠神经系统外在和内在部分的平滑肌细胞和神经结构上。在这个系统中,受体激动剂和拮抗剂直接相互作用以改变兴奋性或抑制性信号。鉴于这种复杂性,我们对影响肠道运动的各种神经激素和药物的作用机制的了解相当零散和不完整也就不足为奇了。然而,最近已经取得了重大进展,基于神经体液受体的肠道运动障碍药物治疗正在兴起。本文对胃肠运动的神经体液调节机制进行了选择性综述。在此背景下,介绍了平滑肌细胞的生理学和药理学、胃肠运动与运动障碍、肠神经系统、胃肠反射和5-羟色胺。进一步研究和了解特别是参与蠕动反射激活的递质和受体对于开发治疗运动障碍的新疗法至关重要。