DIRECT EFFECTS OF COCAINE ON THE PREGNANT HUMAN UTERUS

可卡因对怀孕人类子宫的直接影响

• 批准号: 3461239
• 负责人: WILLIAM W HURD
• 金额: $ 10.34万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3461239
• 关键词: alpha adrenergic receptor; beta adrenergic receptor; calcium channel blockers; catecholamines; cocaine; cyclic AMP; drug abuse; embryo /fetus toxicology; endometrium; human pregnant subject; human tissue; inhibitor /antagonist; inositol phosphates; magnesium; muscle contraction; muscle metabolism; muscle pharmacology; myometrium; oxytocics; oxytocin; pregnancy; premature labor; prostaglandins; radiotracer; receptor binding; tissue /cell culture; tocolytic agents; uterus

Cocaine use in pregnancy is a serious health hazard associated with a premature labor rate of approximately 25%. Unfortunately, little is known about how cocaine might augment uterine contractility and thus cause premature labor. The objectives of this investigation are to determine if cocaine has direct effects on the pregnant human uterus which increase contractility, and to identify the cellular mechanisms of cocaine's effects. The study will have two areas of concentration: First, to determine if cocaine acutely augments the contractile response to various agonists (catecholamines, prostaglandins and oxytocin), uterine strips from pregnant women will be evaluated in vitro using a muscle bath contraction apparatus. Using known tocolytic agents and other probes (alpha- and beta-adrenoceptor agonists and antagonists, prostaglandin inhibitors, calcium-channel blockers, magnesium sulfate), the specific contractile system(s) affected by cocaine, and the most effective way to block these effects will be identified. Chronic cocaine effects will be evaluated by examining uterine strips from pregnant humans who have taken cocaine during their pregnancy. The second area of concentration will be evaluation of the cellular mechanisms of cocaine's effects using slices, minces and membrane preparations of endometrium and myometrium. Cocaine's ability to alter uptake and deactivation will be evaluated by measuring intracellular levels of catecholamines and metabolites after exposure of cells to radiolabeled catecholamines. Cocaine's effect on alpha-adrenoceptors interactions will be evaluated by receptor binding studies, as well as agonist-induced production of prostaglandins and inositol trisphosphate. The acute and chronic effects of cocaine on beta-adrenoceptor function and concentration will be evaluated by receptor binding studies and cyclic AMP assay. Thus, this study will investigate the direct effects of cocaine that increase contractility of the pregnant human uterus and the mechanisms of these effects. This information will help clarify the relationship between cocaine use and premature labor, and provide a rational approach to the treatment of cocaine-associated premature labor.

妊娠期使用避孕药是一种严重的健康危害， 早产率约为25%。 不幸的是， 可卡因是如何增强子宫收缩力 早产 本次调查的目的是确定 可卡因对怀孕的人类子宫有直接影响， 收缩性，并确定可卡因的细胞机制 方面的影响. 该研究将集中在两个领域：首先， 确定可卡因是否急性增强对各种血管的收缩反应， 激动剂（儿茶酚胺、前列腺素和催产素）， 孕妇将在体外使用肌肉浴收缩进行评估， 设备. 使用已知的宫缩抑制剂和其它探针（α-和β-）， β-肾上腺素受体激动剂和拮抗剂，前列腺素抑制剂， 钙通道阻滞剂，硫酸镁），特异性收缩 受可卡因影响的系统，以及阻止这些系统的最有效方法 将确定影响。 慢性可卡因效应将通过以下方式进行评价： 检查怀孕期间服用可卡因的人的子宫条， 他们的怀孕。 第二个重点领域将是评价 可卡因的作用的细胞机制，使用切片，切碎， 子宫内膜和子宫肌层的膜制备。 科摩的能力， 将通过测量细胞内 细胞暴露后的儿茶酚胺和代谢物水平 放射性标记的儿茶酚胺 皮质醇对α-肾上腺素受体的作用 将通过受体结合研究评价相互作用，以及 激动剂诱导的三磷酸肌醇和木菠萝素的产生。 可卡因对β-肾上腺素受体功能的急性和慢性影响 将通过受体结合研究和环AMP 比色法 因此，本研究将调查可卡因的直接影响， 增加怀孕的人类子宫的收缩力， 这些影响。 这些信息将有助于澄清 可卡因使用和早产之间的关系，并提供一个合理的方法， 可卡因相关早产的治疗。