MUSCARINIC RECEPTOR DEVELOPMENT IN ANEURAL HEARTS

拟议研究的目的是为了更好地了解 M-乙酰胆碱受体复合体的研究进展 (MAChR)在心脏组织中的表达，特别是对 受体发育中的副交感神经支配。正常发育 将在雏鸡心脏中研究mAChR的模式，以利用 神经和心肌成分的自然时间分离。这个 将评估神经支配对mAChR发育的影响 在烧灼神经脊区后，导致 心脏神经节。同样，神经节前的影响 副交感神经切除对胆碱能受体系统的研究将在 斜方脑区的切除 节前胞体。联合损伤将去除前期和 心脏副交感神经的节后分支。这个 这些程序的有效性将通过ACH的衡量标准进行评估 心脏组织中胆碱含量和高亲和力胆碱摄取。组织学 检查将显示圆锥干内神经节细胞的数量。 在正常发育和各种实验条件下。 受体复合体特性将使用放射性标记探针进行评估： 受体的数量，它们的激动剂和拮抗剂的结合亲和力， 它们受鸟嘌呤核苷酸的调节，以及它们下调的能力 对暴露于毒鼠宁激动剂的反应将进行测量。这些 实验将提供过多的关于 心脏与其神经的关系，以及生化 心脏组织中胆碱能受体的组织和调节。

The aim of the proposed research is to obtain a better understanding of the development and regulation of muscarinic acetylcholine receptor complexes (mAChR) in cardiac tissues, and in particular the influences of parasympathetic innervation on receptor development. Normal developmental patterns of mAChR will be studied in chick hearts to take advantage of the natural temporal separation of neural and myocardial elements. The influence of innervation on the development of mAChR will be assessed following cauterization of the areas of neural crest which give rise to the cardiac ganglia. Similarly, the influence of preganglionic parasympathectomy on cholinergic receptor systems will be studied after removal of the area of the rhombencephalon which gives rise to preganglionic cell bodies. Combined lesions will remove both pre- and postganglionic branches of parasympathetic innervation of the heart. The effectiveness of these procedures will be assessed through measures of ACh content and high affinity choline uptake in cardiac tissues. Histological examination will reveal the number of ganglion cells in the conotruncus during normal development and in the various experimental conditions. Receptor complex properties will be assessed using radiolabelled probes: The number of receptors, their agonist and antagonist binding affinities, their regulation by guanine nucleotides, and their ability to down regulate in response to exposure to muscarinic agonists will be measured. These experiments will provide a plethora of basic information concerning the relationship of the heart and its nerves, as well as the biochemical organization and regulation of cholinergic receptors in cardiac tissue.