Molecular and Cellular Mechanisms of Alcohol and Anesthetics [antikvár]

Foreword In the last decade it has become evident that ethanol and general anesthetics exert potent effects on cell membranes and membrane-associated functions, such as receptor-ligand interactions, transmembrane signaling, cyclic nucleotide metabolism, and intracellular calcium homeostasis. In this regard, both ethanol and general anesthetics may share common mechanisms of action; yet the two fields of research are often isolated from each other by the very different roles that the drugs play in society and medicine. Alcohol and anesthetics are distinguished from the classical receptor-mediated drugs because they share a nonspecific pharmacology. In 1984, the Third International Conference on Molecular and Cellular Mechanisms of Anaesthetics was held in Calgary, Alberta, and two years later a conference sponsored by the New York Academy of Sciences, entitled Alcohol and the Cell, was held in Philadelphia, Pennsylvania. The organizers of these meetings recognized the need for a joint conference that could address the recent developments in both alcohol and anesthesia research. The objective was to provide an environment for investigators in the two fields to discuss similar and different approaches that have evolved, and thus catalyze further progress in both fields. Major regulatory systems of all cells reside in their membranes, both the enveloping plasma membranes and the internal organelle membranes. It has been known for decades that both ethanol and general anesthetics perturb the phospholipid bilayer of all biological membranes, generally in proportion to their lipid solubility and concentration. This molecular disordering most likely has significant effects on lipid-protein interactions and thereby, on protein functions such as ion flux, receptor binding, and signal transduction. Although the physiological sites of action remain enigmatic, the molecular nature of these sites of action is known to be hydrophobic and relatively insensitive to the structural geometry of the molecule. While major progress has been made in the field of receptor-mediated actions of drugs, the molecular mechanisms underlying the effects of alcohol and anesthetics still remain a mystery. Their actions, although not identical, share many features. It has been generally accepted that their major site of action is at the level of the synapse, but recent research has provided evidence that other channels and even second messenger systems may play a role. Selective effects which have been observed suggest that specific sites may be involved in some actions, and lead to questions regarding a completely unitary or common mechanism. In addition to the acute effects of both alcohol and anesthetics, chronic administration can lead to adaptive changes in the bilayer such that it becomes resistant to molecular disordering. The understanding of these effects may lead to a better understanding of the mechanisms underlying inebriation and anesthesia, as well as functional tolerance, cross-tolerance, and chronic diseases associated with alcoholism. The formal papers and poster sessions at the conference presented results of current research at several levels of system organization and included acute and chronic interactions that described the cellular and molecular mechanisms of action. The present publication is an addition to the monographs of the previous conferences {Molecular and Cellular Mechanisms of Anesthetics, S. Roth and K. W. Miller, Eds. Plenum Publishing Co., 1986; Alcohol and the Cell, E. Rubin, Ed. Ann. N.Y. I