ANANESTHESIA AND AIRWAYS

描述：(改编自申请者的摘要)麻醉放松 部分是通过降低钙敏感性来调节的。 肌细胞(每Cai产生的力)。这项提案中的实验 把重点放在涉及的机制上。调查人员发现， 挥发性麻醉剂减少调节性肌球蛋白光的磷酸化 膜受体刺激支气管平滑肌过程中的链 激动剂。第一个目标是探索麻醉机制 减少rMLC的磷酸化。麻醉药对G蛋白的影响 肌球蛋白轻链磷酸酶的调控将是这一目标的重点。 由于有证据表明，钙敏感性也可能在呼吸道中受到调节 不依赖rMLC磷酸化的平滑肌(可能涉及 酪氨酸激酶)，第二个目标将研究麻醉剂如何影响 丝裂原活化蛋白激酶的酪氨酸磷酸化及其结果 钙调蛋白磷酸化的变化。这些实验将利用两个B 七叶皂甙对犬气管和人支气管平滑肌的通透性 准备工作。在这些制剂中，钙水平可以控制，并且 改变钙敏感性的膜受体第二信使系统 是完好无损的。

DESCRIPTION: (adapted from the applicant's abstract) Anesthetic relaxation of bronchial smooth muscle is in part mediated by decreasing Ca sensitivity of the myocyte (force produced per Cai). The experiments in this proposal focus on the mechanisms involved. The investigators have found that volatile anesthetics decrease phosphorylation of the regulatory myosin light chain during stimulation of bronchial smooth muscle by membrane receptor agonists. The first aim explores anesthetic mechanisms responsible for reduction in rMLC phosphorylation. The effects of anesthetics on G-protein regulation of myosin light chain phosphatase will be focus of this aim. Since there is evidence that Ca sensitivity may also be regulated in airway smooth muscle independent of rMLC phosphorylation (possibly involving tyrosine kinases), the second aim will investigate how anesthetics affect tyrosine phosphorylation of mitogen-activated protein kinases and consequent changes in caldesmon phosphorylation. These experiments will utilize both B escin permeabilized canine tracheal and human bronchial smooth muscle preparations. In these preparations, calcium levels can be controlled, and membrane receptor second messenger systems that alter calcium sensitivity are intact.