EFFECTS OF ANTICONVULSANTS ON GLIAL CELL ION TRANSPORT

抗惊厥药对胶质细胞离子运输的影响

• 批准号: 3404317
• 负责人: H Steve WHITE
• 金额: $ 10.54万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3404317
• 关键词: acetazolamide; acid base balance; adenosinetriphosphatase; anions; anticonvulsants; carbamazepine; carbonate dehydratase; cations; cell biology; central nervous system; drug metabolism; electrolyte balance; electrophysiology; generalized seizures; glia; homeostasis; ion transport; membrane permeability; membrane potentials; neural information processing; neurochemistry; newborn animals; phenytoin; scintillation counter; tissue /cell culture; valproate

The specific aims of this research proposal are to determine the effects that the anticonvulsants phenytoin, carbamazepine, valproic acid, ethosuximide, acetazolamide, and diazepam have on cation and anion transport processes and intracellular pH homostasis of glial cells isolated from the cerebral cortices of 3-day old neonatal rats and maintained in isolated tissue culture. They include determination of the acute and chronic effects of each agent on: (1) the DNA and protein content of treated cultures, (2) the activity of the transport enzymes Na+/K+, Ca++/Mg++, and HCO3-ATPase, (3) the concentration of intracellular Na+, K+, and Cl, and ion flux measurements, (4) the activity of the glial specific enzyme carbonic anhydrase, (5) the membrane potential, resistance and conductance, (6) the intracellular pH, (7) the effect of specific inhibitors of cation and anion transport in the presence and absence of anticonvulsant drugs, (8) the effect of increasing extracellular K+, and (9) the effect of pentylenetetrazol alone and with each anticonvulsant agent. These studies will involve the disiplines of neuropharmacology, biochemistry, electrolyte and acid-base chemistry, eletrophysiology, cellular biology, and isolated tissue culture. The experiments are designed to test the hypothesis that changes in these parameters will enhance glial cell regulatory process thereby providing the CNS with an enhanced ability to regulate the extracellular fluid. Such experiments are important, for if a thorough understanding of the mechanisms of these drugs is to be obtained, a comprehensive examination of their effects on glial cells as well as neurons must be undertaken. When the mechanisms of these anticonvulsants are determined, new drugs exhibiting similar characteristics but with fewer side-effects can be made and tested for clinical efficacy.

该研究建议的具体目的是确定影响 抗惊厥药苯妥英，卡马西平，丙戊酸， 阳离子和阴离子具有硫代胺，乙唑胺和地西ep剂 分离的神经胶质细胞的转运过程和细胞内pH均率 从3天老新生大鼠的脑皮质中 分离的组织培养。 它们包括确定急性和 每种药物的慢性影响：（1）DNA和蛋白质含量 处理过的培养物，（2）转运酶Na+/K+的活性， Ca ++/mg ++和HCO3-ATPase，（3）细胞内Na+，K+， （4）胶质特异性的活性 酶碳酸酐酶，（5）膜电势，电阻和 电导，（6）细胞内pH，（7）特定的影响 在存在和不存在的情况下，阳离子和阴离阴离子的抑制剂 抗惊厥药，（8）增加细胞外K+的作用 （9）单独使用戊基环唑和每种抗惊厥药的效果 代理人。 这些研究将涉及神经药理学的疾病， 生物化学，电解质和酸碱化学，el骨生理学， 细胞生物学和分离的组织培养。 实验是 旨在测试这些参数的变化的假设 增强神经胶质细胞调节过程，从而为CNS提供 增强了调节细胞外流体的能力。 这样的实验是 重要的是，如果对这些药物的机制有透彻的理解 要获得，对它们对神经胶质的影响进行了全面检查 必须进行细胞和神经元。 当这些机制 确定抗惊厥药，新药表现出相似的 特征但可以进行较少的副作用，并测试 临床功效。