We propose an anesthesiology research center, consisting of six closely-interrelated research projects, supported by a core facility and focused on Fundamental Mechanisms of Actions of Anesthetic and Analgesic Drugs. This will be a multidisciplinary, collaborative effort of basic laboratory scientists and clinicians, aimed at uncovering underlying mechanisms of action and promoting the application of these fundamental research findings to clinical problems. Through the Center mechanism, we will coordinate research groups working at different levels of organization on problems relating to the interaction of anesthetics with excitable tissues. The concepts and mechanisms elucidated through basic studies at molecular and biochemical levels in well-defined systems will find application in the applied pharmacology of other Center investigators. The six research projects are: 1. Gram Negative Peritonitis and Endogenous Opioid Peptides 2. Calcium Metabolism in Malignant Hyperthermia 3. Mechanisms of Action of General Anesthetics and Pressure at Cholinergic Synapses 4. Effects of Anesthetics of Membrane Structure as Determined by Phospholipid Exchange Proteins. 5. Regulation of the Adenylate Cyclase System 6. Mechanism and Site of Action of Anesthetics Blocking Nerve Conduction.
