ANANESTHESIA AND AIRWAYS

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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.