Cardiac Opioid Receptor Activation and Protein Kinase C

心脏阿片受体激活和蛋白激酶 C

• 批准号: 6842220
• 负责人: Easton A. Reid
• 金额: $ 1.77万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6842220
• 关键词: biological signal transduction; calcium; cardiac myocytes; confocal scanning microscopy; heart contraction; immunocytochemistry; immunofluorescence technique; laboratory rat; myocardium; opioid receptor; postdoctoral investigator; protein isoforms; protein kinase C; protein transport; receptor coupling; receptor expression; western blottings

DESCRIPTION (provided by applicant): Opioid receptors belong to the family of G-protein coupled receptors (GPCRs) with seven transmembrane regions spanning the sarcolemmal membrane and are coupled to inhibitory G-proteins which activate hospholipase C (PKC) and protein kinase C (PKC). One or multiple PKC isoforms translocate from the cytosol to target membranes where phosphorylation of serine/threonine residues cause a cascade of myocyte protective events. To date, the effects of cardiac opiate receptor subtype activation and their intracellular signaling mechanisms in normal and ischemic myocardium have been conflicting. This training proposal will determine opioid receptor subtype modulation of cardiac myocyte excitation-contraction coupling via specific PKC isoforms. Specific aims will: 1) determine delta- and kappa-opioid receptor modulation of cardiac excitation-contraction coupling in intact myocardium and 2) determine opioid receptor mediated PKC isoform signaling and modulation of intracellular calcium.

描述（由申请人提供）：阿片受体属于g蛋白偶联受体（gpcr）家族，具有跨越肌层膜的7个跨膜区域，并与激活磷脂酶C （PKC）和蛋白激酶C （PKC）的抑制性g蛋白偶联。一个或多个PKC异构体从细胞质转移到靶膜，丝氨酸/苏氨酸残基的磷酸化引起一系列肌细胞保护事件。迄今为止，心脏阿片受体亚型激活及其细胞内信号传导机制在正常和缺血心肌中的作用一直存在争议。该训练方案将通过特定PKC亚型确定阿片受体亚型对心肌细胞兴奋-收缩偶联的调节。具体目的将包括：1)确定完整心肌中δ -和kappa-阿片受体对心脏兴奋-收缩耦合的调节；2)确定阿片受体介导的PKC异构体信号传导和细胞内钙的调节。