Permeation of narcotics

Direct determinations of the adsorption of ethylene on egg albumin, urease, sodium oleate, and other sols have been made by Nord and his associates (Ola). These show that only in the case of the sodium oleate is tlic adsorption conspicuous, although they do not completely exclude adsorption on egg albumin, or on untested cellular enzymes. The indirect evidence from the increase in surface tension and the decrease in viscosity of colloids produced by ethylene suggests that adsorption occurs. But ethylene is considered not to show resonance (69a), a prerequisite for the presence of the polarized form suggested by Nord and Franke (63a, 63b) as the basis for its adsorption. It seems still undecided whether or not ethylene is adsorbed at strategic positions on any of the cellular fermentation enzymes. The increased carbon dioxide production in the presence of an ethylene film is well established by Nord et al. (62a, 62b, 63, 63a, 63b) but there is less evidence as to the manner of action of ethylene. 

The manner of action of narcotics has been discussed extensively, and some of these discussions are relevant to permeability. The adsorption theory of Traube (86) has not proved to be successful in many cases. It seems questionable for ethylene, for reasons just discussed, and probably for the action of ethylene on permeability. The lipoid theory of narcotics has been advanced by Overton (69) and Meyer (52), and seems stronger. It depends on the correlation between narcotic effect and the distribution coefficients between lipides and water. Those narcotics with higher solubilities in lipides have been widely found to have higher narcotic effects. 

This is important for permeability, since plasma membranes appear to contain a high proportion of lipides, as shown, e.gr., for erythrocytes by Dziemian (18). Ethylene would be able, by virtue of its apolar structure, to dissolve in the lipide phase and to counteract the bonding effect of the double bonds of the lipide hydrocarbon chains. At first, however, the presence of additional apolar molecules may account for the frequently observed decrease in permeability, while the ultimate invasion of the membrane by ethylene would disrupt it, with increased permeability. This permeability is here thought of as applying to glucose and other molecules highly soluble in water. 

This terminal increase in permeability has often been found to be irreversible, and this irreversibility is generally acknowledged. The increase noted by Nord (62a,62b), and Nord and Franke (63,63a,63b) may form an exception, in that this effect disappears after 30-60 minutes or more. Alternatively it may be concluded that the increase is quasi-permanent, while inhibition of the cell enzymes supervenes, thus concealing the effects of permeability changes. The inhibition by ethylene of the zymase activity of cell-free yeast extracts shows that decrease in cellular permeability is at most of only minor importance. 

Effect of urethan on oxygen consumption by yeast (23). The ordinate is the logarithm of the ratio of the uninhibited to the inhibited oxygen consumption. Three runs are represented by different symbols large croeaes are theoretical points. 

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