THEOPHYLLINE/SKELETAL MUSCLE CONTRACTION AND ENERGY BALANCE

茶碱/骨骼肌收缩和能量平衡

• 批准号: 3734877
• 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/3734877
• 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， 被人类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 对低剂量的甲基黄嘌呤（尤其是咖啡因）不敏感， 茶碱，但肌肉收缩特性的改变已经被 常规观察咖啡因和茶碱剂量相当于 在喝咖啡和接受治疗的人身上发现的。 因此 这项工作的目的是，在学生的帮助下，调查 高和低茶碱水平对肌肉收缩作用 代谢稳定的哺乳动物肌肉模型中的能量平衡。 为 为此目的，将使用大鼠的分离的比目鱼肌和EDL肌肉。 茶碱诱发的抽搐增强和痉挛剂量反应 将确定两种分离制备物的曲线。 此外，本发明还提供了一种方法， 茶碱对这些肌肉中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。 的 然后将茶碱的结果与先前的结果进行比较 以确定是否存在任何差异， 这两种甲基黄嘌呤对肌肉收缩的作用。 更清楚 茶碱的直接肌肉作用的图片应该出现，包括 如果茶碱像咖啡因一样能直接作用于四肢肌肉 治疗水平的收缩。 同时，通过使用钙 激动剂/拮抗剂来改变茶碱的作用，更好的 对茶碱在骨骼肌中作用机制的认识 肌肉应该出现。 学生助理将能够参与 在各个方面。 他们将获得标准生理学和心理学方面的经验， 以及生物化学技术和通过其他支持活动， 鼓励从事生物医学研究事业。