Millhorn D E, Bayliss D A, Erickson J T, Gallman E A, Szymeczek C L, Czyzyk-Krzeska M, Dean J B
Department of Physiology, University of North Carolina, Chapel Hill 27599.
Am J Physiol. 1989 Dec;257(6 Pt 1):L289-310. doi: 10.1152/ajplung.1989.257.6.L289.
During the last decade much progress has been made in understanding the cellular and molecular mechanisms by which nerve cells communicate with each other and nonneural (e.g., muscle) target tissue. This review is intended to provide the reader with an account of this work. We begin with an historical overview of research on cell-to-cell communication and then discuss recent developments that, in some instances, have led to dramatic changes in the concept of synaptic transmission. For instance, the finding that single neurons often contain multiple messengers (i.e., neurotransmitters) invalidated the long-held theory (i.e., Dale's Law) that individual neurons contain and release one and only one type of neurotransmitter. Moreover, the last decade witnessed the inclusion of an entire group of compounds, the neuropeptides, as messenger molecules. Enormous progress has also been made in elucidating postsynaptic receptor complexes and biochemical intermediaries involved in synaptic transmission. Here the development of recombinant DNA technology has made it possible to clone and determine the molecular structure for a number of receptors. This information has been used to gain insight into how these receptors function either as a ligand-gated channel or as a G protein-linked ligand recognition molecule. Perhaps the most progress made during this era was in understanding the molecular linkage of G protein-linked receptors to intramembranous and cytoplasmic macromolecules involved in signal amplification and transduction. We conclude with a brief discussion of how synaptic transmission leads to immediate alterations in the electrical activity and, in some cases, to a change in phenotype by altering gene expression. These alterations in cellular behavior are believed to be mediated by phosphoproteins, the final biochemical product of signal transduction.
在过去十年中,我们在理解神经细胞之间以及神经细胞与非神经(如肌肉)靶组织之间进行通讯的细胞和分子机制方面取得了很大进展。这篇综述旨在向读者介绍这项工作。我们首先对细胞间通讯的研究进行历史概述,然后讨论近期的进展,这些进展在某些情况下已导致突触传递概念发生了巨大变化。例如,发现单个神经元通常含有多种信使(即神经递质),这使得长期以来的理论(即戴尔定律)失效,该理论认为单个神经元只含有并释放一种且仅一种类型的神经递质。此外,在过去十年中,一组完整的化合物——神经肽,被纳入信使分子的范畴。在阐明突触后受体复合物以及参与突触传递的生化中介方面也取得了巨大进展。在这里,重组DNA技术的发展使得克隆和确定多种受体的分子结构成为可能。这些信息已被用于深入了解这些受体如何作为配体门控通道或作为G蛋白偶联配体识别分子发挥作用。也许这个时代取得的最大进展是在理解G蛋白偶联受体与参与信号放大和转导的膜内及细胞质大分子的分子联系方面。我们最后简要讨论突触传递如何导致电活动的即时改变,以及在某些情况下如何通过改变基因表达导致表型变化。这些细胞行为的改变被认为是由磷蛋白介导的,磷蛋白是信号转导的最终生化产物。