THEOPHYLLINE/SKELETAL MUSCLE CONTRACTION AND ENERGY BALANCE

茶碱/骨骼肌收缩和能量平衡

• 批准号: 3756457
• 负责人: ELIZABETH T HAYS
• 金额: --
• 依托单位: BARRY UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3756457
• 关键词: Anura; bioenergetics; calcium channel blockers; dosage; drug adverse effect; drug interactions; electrophysiology; laboratory rat; microspectrophotometry; muscle contraction; phosphates; striated muscles; theophylline

Methylxanthines, as caffeine and theophylline, are frequently ingested by humans, used as therapeutic agents and used as experimental tools. The contraction of mammalian skeletal muscle was thought to be relatively insensitive to low doses of methylxanthines, particularly caffeine and theophylline, but alterations in muscle contraction properties have been routinely observed with caffeine and theophylline doses equivalent to those found in humans ingesting coffee and on therapeutic regimens. Thus an aim of this work is, with the assistance of students, to investigate the action of both high and low theophylline levels on muscle contraction and energy balance in metabolicly-stable mammalian muscle models. For this purpose isolated soleus and EDL muscles of the rat will be used. Theophylline-evoked twitch potentiation and contracture dose response curves will be ascertained for both isolated preparations. In addition, theophylline's effect on high energy phosphate levels in these muscles will be compared to effects obtained in frog skeletal muscle. The results with theophylline will then be compared with results previously obtained with caffeine to determine if any differences exist in the action of these two methylxanthines on muscle contraction. A clearer picture of direct muscle actions of theophylline should emerge, including if theophylline, like caffeine, can exert a direct effect on limb muscle contraction at therapeutic levels. Also, by using calcium agonists/antagonists to modify theophylline's action, a better understanding of the mechanism of theophylline's action in skeletal muscle should emerge. Students assistants will be able to participate in all aspects. They will gain experience in both standard physiological as well as biochemical techniques and via other supportive activities be encouraged to pursue biomedical research careers.

甲基黄嘌呤，如咖啡因和茶碱，经常被摄取 由人类使用，用作治疗剂和实验工具。 哺乳动物骨骼肌的收缩被认为是相对 对低剂量甲基黄嘌呤不敏感，特别是咖啡因和 茶碱，但肌肉收缩特性的变化 常规观察咖啡因和茶碱的剂量相当于 在人类摄入咖啡和治疗方案中发现的那些。因此， 这项工作的一个目的是，在学生的帮助下，调查 茶碱高低对肌肉收缩的作用 代谢稳定的哺乳动物肌肉模型中的能量平衡。为 为此，将使用大鼠的比目鱼肌和EDL肌。 茶碱诱发的抽动增强与肌挛缩量效关系 将确定两种分离制剂的曲线。此外, 茶碱对这些肌肉高能磷酸盐水平的影响 将与在青蛙骨骼肌中获得的效果进行比较。这个 然后将茶碱的结果与之前的结果进行比较 用咖啡因获取，以确定在 这两种甲基黄嘌呤对肌肉收缩的作用。一个更清晰的 茶碱的直接肌肉动作图应该出现，包括 如果茶碱和咖啡因一样，对四肢肌肉有直接作用 在治疗水平上的收缩。此外，通过使用钙 激动剂/拮抗剂修改茶碱的作用，更好 对茶碱在骨骼中作用机制的认识 肌肉应该会长出来。学生助教将能够参与 在各个方面。他们将获得两个标准生理学方面的经验 以及生化技术和其他支持活动 鼓励从事生物医学研究事业。