PHARM & DISTRIBUTION OF A CARDIOEXCITATORY NEUROPEPTIDE

医药

• 批准号: 3485932
• 负责人: MICHAEL J GREENBERG
• 金额: $ 8.69万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-06-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3485932
• 关键词: Bivalvia; Crocodilia; Echinodermata; Gastropoda; Mollusca; Tunicata; amides; aminoacid analyzer; aquatic biology; atrial natriuretic peptide; cardiotonic agents; chemical structure function; fish; ganglions; heart pharmacology; high performance liquid chromatography; immunochemistry; laboratory rabbit; laboratory rat; neurons; neuropeptides; neurotransmitter receptor; radioimmunoassay; radiotracer; vascular smooth muscle

The molluscan cardioexcitatory peptide FMRFamide (Phe-Met- Arg-Phe-NH2), together with four structurally similar peptides, constitute a closely related nuclear family which now includes among its membership two tetrapeptides and three heptapeptides. The tetra-and heptapeptides have different phyletic distributions among the molluscs, and have distinctive effects and receptors on muscles and nerves. Antisera to FMRFamide also cross-react widely with antigens in the nerve and endocrine cells of non- molluscan groups, both vertebrate and invertebrate. Some of this immunoreactivity is due to established peptides, but previously unknown peptides have also been discovered. These immunochemical results are manifestations of a large, heterogeneous, widespread, extended peptide family; it is characterized by an amidated C-terminal dipeptide of the form Arg-X-NH2 (where X is an aromatic residue). The first long-term goal of this project is to examine the tissue distributions, actions and physiological roles of the individual FMRFamide-related peptides (FaRPs) making up the model nuclear family in the pulmonate snail, Helix aspersa. The receptors complementary to the FaRPs will be characterized by studying the structure- activity relations (SAR) of these peptides on whole tissues, biochemical mechanisms, and radioligand-receptor binding properties. The variation in the levels and potency of the FaRPs, as a function of the activity state of the snails will also be examined. The second long-term goal is to determine the phyletic distribution, size, and limits of the extended family of FaRPs, and to define its relationship with the nuclear family in molluscs. New extra-molluscan FaRPs will be sought in central nervous extracts of vertebrates and key invertebrates. The effects, of both the nuclear and extended FaRPs, on vertebrate vascular smooth muscle will be tested and the receptors characterized by SAR. The relationship between the nuclear family of FaRPs and the extended family may reside in the homology of their receptors; the similarities between the peptides themselves are probably due to convergence.

软体动物心脏兴奋肽 FMRFamide (Phe-Met- Arg-Phe-NH2) 以及四种结构相似的肽， 构成了一个密切相关的核心家庭，其中包括 其成员中有两种四肽和三种七肽。 四肽和七肽具有不同的系统分布 在软体动物中，具有独特的作用和受体 肌肉和神经。 抗血清与 FMRFamide 也会发生交叉反应 广泛存在于非神经细胞和内分泌细胞中的抗原 软体动物群体，包括脊椎动物和无脊椎动物。 其中一些 免疫反应性是由于已建立的肽，但之前 还发现了未知的肽。 这些 免疫化学结果是大量的表现， 异质的、广泛的、扩展的肽家族；这是 其特征在于酰胺化的 C 末端二肽，形式为 Arg-X-NH2（其中X是芳族残基）。 第一个长期 该项目的目标是检查组织分布、行为 和个体 FMRFamide 相关的生理作用 构成模型核心家族的肽（FaRP） 肺蜗牛，Helix aspersa。 受体互补 FaRP 将通过研究结构来表征- 这些肽在整个组织上的活性关系（SAR）， 生化机制和放射性配体-受体结合 特性。 FaRP 水平和效力的变化， 作为蜗牛活动状态的函数也将是 检查了。 第二个长期目标是确定种系 FaRP 大家族的分布、规模和限制，以及 定义其与软体动物核心家族的关系。 将在中枢神经中寻找新的软体动物外 FaRP 脊椎动物和主要无脊椎动物的提取物。 的影响， 脊椎动物血管上的核 FaRP 和延伸 FaRP 将测试平滑肌并表征其受体 特别行政区。 FaRP 核心家族与 大家庭可能存在于他们的同源性中 受体；肽本身之间的相似之处是 可能是由于收敛。