EFFECTS OF REPRODUCTIVE PEPTIDES ON NEURONS

生殖肽对神经元的影响

• 批准号: 3406398
• 负责人: JAMES E BLANKENSHIP
• 金额: $ 4.06万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3406398
• 关键词: chemical structure function; egg /ovum; electrophysiology; hormone regulation /control mechanism; invertebrate hormone; microelectrodes; neuroendocrine system; peptide hormone; synthetic peptide

The neuroendocrine bag cells of Aplysia and the reproductive organ called the atrial gland produce a family of closely related peptides which are involved in the initiation and regulation of egg-laying behavior in this animal. Some of the peptides from both sources cause egg release from the gonad and also have directed effects on identified case cells: bag cell egg-laying hormone (ELH) acts directly on the gonad and also excites cell R15; Alpha-bag cell peptide (Alpha-BCP) causes inhibition of the left upper quadrant (LUQ) cells and also excites the bag cells. Atrial gland peptides A and B, portions of which are homologous to Alpha-BCP, also excite the bag cells. The atrial gland peptide, egg-releasing hormone (ERH), ehich is partially homologus to both ELH and peptides A and B, can both act on the gonad and cause excitation of the bag cells. The atrial gland releases several other biologically active peptides, causing either egg laying, bag cell firing, or both, but their ability to affect other neurons has not been tested. We have shown that Alpha-BCP inhibits cells R2, R3-R13, and L10 (interneuron I), and that atrial gland extracts excite the LUQ cells and R2, effects opposite to those caused by the bag cells. Using synthetic peptides or peptide fragments of closely homologous molecules, such as Alpha-BCP and the 9-amino acid C-terminal portion of peptide B (B26-34), we have found that differences in only a few amino acid residues can result in a selective loss of effects: while both Alpha-BCP and peptide B can excite the bag cells, B26-34 only weakly sitmulates Alpha-BCP's inhibitory effect on the LUQ cells. We propose to extend these studies using intracellular electrophysiological and pharmacological techniques, measuring voltage, current and conductance changes in a wide variety of Aplysia neurons, to determine the mechanism of action, ionic dependence, the active site, and the structure-activity relations of several natural and synthetic peptides (or fragments/analogues of them), including ELH, peptide B, ERH and Alpha-BCP. Peptides will be administered by either bath superfusion, arterial perfusion, or localized pressure ejection from microelectrodes. These studies will provide new information about the neural effects of many of the bag cell and atrial gland peptides, and also reveal how alterations in primary structure of neuroactive peptides can influence their mode of action.

Aplysia的神经内分泌袋细胞和生殖器官称为 心房产生一个密切相关的肽家族 参与了卵子上卵行为的启动和调节 动物。 两种来源的某些肽导致卵从 性腺，还对已识别的病例细胞有指示的影响：袋细胞 卵激素（ELH）直接作用在性腺上，还激发了细胞 R15; α-bag细胞肽（α-BCP）会抑制左上方 象限（LUQ）细胞，还激发了袋细胞。 心房腺肽 A和B，其中部分与Alpha-BCP同源，也激发了袋子 细胞。 心房肽，卵激素（ERH），Ehich是 对ELH和肽A和B的部分同源物都可以对 性腺并引起袋细胞的激发。 心房释放 其他几种具有生物活性肽，导致卵子铺设，袋子 细胞发射，或两者兼而有之，但它们影响其他神经元的能力尚未 已被测试。 我们已经表明，α-BCP抑制细胞R2，R3-R13和 l10（interneuron i），而心房腺提取引起了LUQ细胞 和R2，与袋细胞引起的效果相反。 使用合成 紧密同源分子的肽或肽片段，例如 Alpha-BCP和肽B的9-氨基酸C末端部分（B26-34），我们 已经发现，只有少数氨基酸残基的差异会导致 选择性效果丧失：虽然α-BCP和肽B都可以激发 B26-34袋细胞仅弱地坐着α-BCP的抑制作用 在LUQ细胞上。 我们建议使用细胞内扩展这些研究 电生理和药理技术，测量电压， 电流和电导的多种神经元的变化， 确定作用机理，离子依赖性，主动位点和 几种天然和合成肽的结构活性关系 （或它们的片段/类似物），包括ELH，肽B，ERH和 alpha-bcp。 肽将通过任何一个浴超级灌注来施用， 动脉灌注或微电极的局部压力排斥。 这些研究将提供有关许多人的神经效应的新信息 袋细胞和心房腺肽的含量，也揭示了如何改变 在神经活性肽的主要结构中，可以影响其 行动。