GLUCOSE AND OXYGEN UTILIZATION IN SYMPATHETIC GANGLIA 119 



tion. But the overall, steady state effect gives a net increase in the ATP concen- 

 tration. One can do a pilot experiment on oxidative phosphorylation which 

 shows the type of trouble one can get into when you do P/O ratios. In oxidative 

 phosphorylation one stimulates the system by adding glucose and hexokinase. 

 This means that you can then pick up very sensitively any decrease in net pro- 

 duction of ATP by measuring phosphate uptake. If, however, you leave out 

 hexokinase and glucose and detect ATP formation directly, than it takes much 

 larger concentrations of narcotics to give you a reduction in the ATP concen- 

 tration in your preparations. This merely reflects again the concentration of 

 the receptor systems. 



There is one other thing, in this work we are talking about molecular struc- 

 ture and there is, as you know, a whole host of data from various sources indi- 

 cating certain physical-chemical relationships between structure and biological 

 activity. If oxidative phosphorylation is important as at least one site of action 

 of the narcotics, one might expect to find the same physico-chemical relation- 

 ships with mitochondria as with the whole organism. What we have been trying 

 to do is to take some of these unique narcotics, namely, those whose partition 

 coefficients decrease with a rise in temperature and those whose physiological 

 effects decrease with a rise in temperature and determine their effect on oxida- 

 tive phosphorylation at different temperatures. If one starts out with a concen- 

 tration of salicylamide which gives 50% uncoupling at 15°, one finds that there 

 is no uncoupling at 35°C, whereas with chloretone the inhibition of the P/O 

 ratio increases with a rise of temperature. There is one other property which 

 Johnson emphasized and that is the reversing of narcotic effect in tadpoles by 

 high pressure. One can also show a reversal of inhibition of phosphate uptake 

 by barbiturates by high pressure. Therefore, in terms of molecular structure 

 and activity one can find in the mitochondria the same physico-chemical rela- 

 tionships. But I think it is quite clear from the analysis in the intact animal 

 that this is not the only explanation for the mechanism of action of the narcotic. 

 There is, certainly, something else going on on the other side and what this is, 

 I think, is anybody's guess. 



Chairman Gerard : Dr. Fischer, would you like to reopen your paper? 



Dr. Fischer: I would like to answer some of the still-open questions. 



I would like equally to emphasize the importance of the forces of attraction 

 and those of the binding of substances to wool. Remember, as an example, 

 that you cannot kiss effectively if you do not embrace a person well. What is 

 not generally recognized is that the attraction of a basic dye is stronger the 

 more basic the dye (electrostatic effect) but the binding which takes place 

 once the dye is attracted is generally believed to be due mainly to hydrogen 

 bonding. 



I am not so much concerned about the fact that according to some authors 



