The Influence of Minimal Narcotic Doses on the Respiration of Erythrocytes by Walter Fleischmann and Charles S. Rand

The investigations of Warburg in 1921 on the action of narcotics on cell respiration led to the formulation of his general theory of narcosis, according to which the action of a narcotic is attributed to its specific ability to occupy the vital surfaces of the cell structures, thereby displacing the adsorbed nutritive substances and important oxidative enzymes (1). The occasional observations of some investigators, describing a stimulating action of narcotics on the metabolic functions of the cell, seem hardly compatible with Warburg's theory; for, "adsorption displacement," as Warburg calls the phenomenon, might bring about a depression, but not a stimulation of cellular metabolism. In his experiments on the respiration of the isolated spinal cord of the frog under the influence of ethyl alcohol, Winterstein (2) describes a series of cases in which low concentrations of this narcotic produced acceleration, higher concentrations, on the other hand, produced metabolic depression. Similar results were obtained by Garrey (3) in his experiments on the stimulating effect of ethyl alcohol on the CO~ production of the heart ganglia of Limulus polyphemus. Warburg, who made similar investigations on liver cells, avian erythrocytes, and the central nervous system, could find no such acceleration. Narcotic concentrations lower than those which caused metabolic depression were without effect. In explanation of this discrepancy between his results and those of other investigators, Warburg suggested (9) that metabolic acceleration would result upon administering a narcotic to starving ceils. The narcotic would then play the r61e of a nutritive substance and as such might be replaced by glucose or peptone with the same stimulating effect. Of course, in the case of cells such as sea urchin eggs, where lipoid-soluble substances serve as a stimulus to further development, as was first demonstrated by Jacques Loeb, an