PHARMACOLOGY OF CARDIOEXCITATORY NEUROPEPTIDES

FMRFamide（Phe-Met-Arg-Phe-NH 2）是从蛤类中分离得到的一种神经肽 神经节;它储存在颗粒中，并在去极化时释放。 FMRFamide是一种有效的软体动物药物：它是心脏兴奋性的， 抑制性取决于物种;它会导致各种肌肉挛缩 并影响神经元活动。 FMRFamide仅是一组实施例中的一个示例。 异源但结构和功能同源软体动物 神经肽 此外，假设FMRFamide样肽 广泛分布于动物中，包括脊椎动物， 在蛋白质进化中与阿片肽有着共同的起源。 这 该项目的重点是物种分布和作用机制， FMRFamide。 首先，三种肽，已经在大脑中发现， 腹足类，Busycon contrarium和Haplaspersa，将进一步纯化 通过高效液相色谱法， 组成和序列确定。 提取纯化 将通过FMRFamide（Busycon radula）特异性生物测定监测步骤 保护肌）或阿片肽（豚鼠回肠和小鼠输精管 deferens）。 也将在其他组织中寻找FMRFamide样肽： 猪肾上腺髓质和交感神经节;以及中央神经节 与其他无脊椎动物门的区别 由于这些肽被表征，它们的 将确定亚细胞定位，并通过钾离子释放 将演示去极化。 一种颗粒结合肽酶， 已提出FMRFamide的N-末端扩展前体;尝试 FMRFamide受体将被表征， 通过对特定软体动物心脏和肌肉的结构-活性研究 和兔血管平滑肌的作用，所选制剂为 敏感的肽;和他们的反应超出其范围 方面的影响. FMRFamide的变力作用与其 对环核苷酸水平的作用。 蔗糖间隙技术将是 用于关联电和机械响应。

FMRFamide (Phe-Met-Arg-Phe-NH2) is a neuropeptide isolated from clam ganglia; it is stored in granules, and released upon depolarization. FMRFamide is a potent molluscan pharmacon: it is cardioexcitatory or inhibitory depending on species; it causes contractures of various muscles and affects neuronal activity. FMRFamide is only one example of a set of heterogenous, but structurally and functionally homologous, molluscan neuropeptides. Moreover, it is hypothesized that FMRFamide-like peptides are widely distributed among animals, including vertebrates, and may have had a common origin with the opioid peptides in protein evolution. This project focuses on the phyletic distribution and mechanisms of action of FMRFamide. First, three peptides, already identified in the brains of the gastropods, Busycon contrarium and Helix aspersa, will be further purified by high performance liquid chromatography, and their amino acid compositions and sequences determined. The extraction and purification steps will be monitored by bioassays specific for FMRFamide (Busycon radula protactor muscle) or of the opioid peptides (guinea-pig ileum and mouse vas deferens). FMRFamide-like peptides will also be sought in other tissues: porcine adrenal medulla and sympathetic ganglia; and the central ganglia from other invertebrate phyla. As these peptides are characterized, their subcellular localization will be determined, and their release by potassium depolarization will be demonstrated. A particle-bound peptidase, coverting N-terminal extended precursors to FMRFamide, has been proposed; an attempt will be made to demonstrate it. FMRFamide receptors will be characterized by structure-activity studies on particular molluscan hearts and muscles and on rabbit vascular smooth muscle; the selected preparations are sensitive to the peptide; and their responses exemplify the range of its effects. The inotropic effects of FMRFamide will be correlated with its actions on cyclic nucleotide levels. The sucrose gap technique will be used to correlate electrical and mechanical responses.