PHARMACOLOGY OF A CARDIOEXCITATORY NEUROPEPTIDE

心脏兴奋性神经肽的药理学

• 批准号: 2216284
• 负责人: MICHAEL J GREENBERG
• 金额: $ 13.72万
• 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 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2216284
• 关键词: Bivalvia; Crocodilia; Echinodermata; Gastropoda; Mollusca; Tunicata; alternatives to animals in research; 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; proteins; 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-Phe）是一种新型的心脏兴奋肽。 Arg-Phe-NH 2）与四种结构相似的肽一起， 组成了一个紧密联系的核心家庭，现在包括 在其成员中有两个四肽和三个七肽。 四肽和七肽具有不同的系统分布 在软体动物中，有独特的作用和受体， 肌肉和神经。 抗FMRFamide的抗血清也与 广泛存在于神经和内分泌细胞中的抗原， 脊椎动物和无脊椎动物的软体动物群体。 其中一些 免疫反应性是由于建立肽，但以前 还发现了未知的肽。 这些 免疫化学结果是一个大的， 异质的，广泛的，扩展的肽家族;它是 其特征在于酰胺化的C-末端二肽， Arg-X-NH 2（其中X是芳族残基）。 第一长期 本项目的目标是检查组织分布，行为 与FMRFamide相关的个体的生理作用 肽（FaRPs）组成的模型核家庭中， 有肺蜗牛，Hespersa。 受体互补于 FaRP将通过研究结构来表征- 这些肽对整个组织的活性关系（SAR）， 生化机制和放射性配体-受体结合 特性. FaRP的水平和效力的变化， 作为蜗牛活动状态的函数， 考察 第二个长期目标是确定 FaRP大家族的分布、大小和限度，以及 来定义它与软体动物核心家庭的关系。 将在中枢神经系统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， 无论是核和扩展FaRPs，对脊椎动物血管 将测试平滑肌，并且受体的特征在于： 特别行政区 FaRPs核心家族与 该扩展家族可以存在于它们的同源性中， 受体;肽本身之间的相似性是 可能是因为趋同。