MUSCARINIC RECEPTOR DEVELOPMENT IN ANEURAL HEARTS

拟议研究的目的是为了更好地了解 毒蕈碱型乙酰胆碱受体复合物的形成和调节 （mAChR）在心脏组织中的作用，特别是 副交感神经支配对受体发育的影响 正常发育 将在鸡心脏中研究mAChR的模式， 神经和心肌元素的自然时间分离。 的 将评估神经支配对mAChR发育的影响 在烧灼神经嵴区域后， 心脏神经节 类似地，节前神经元的影响 将研究副交感神经切除术对胆碱能受体系统的影响， 切除引起以下症状的菱脑区域 节前细胞体 联合病变将切除术前和术后 心脏的副交感神经支配的节后分支。 的 这些程序的有效性将通过ACh的措施进行评估 含量和高亲和力胆碱摄取。 组织学 检查将显示圆锥干中神经节细胞的数量 在正常发育和各种实验条件下。 将使用放射性标记探针评估受体复合物特性： 受体的数量，它们的激动剂和拮抗剂结合亲和力， 它们通过鸟嘌呤核苷酸进行调节， 将测量对暴露于毒蕈碱激动剂的反应。 这些 实验将提供大量的基本信息， 心脏和神经的关系，以及生物化学 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.