GLUCOSE AND OXYGEN UTILIZATION IN SYMPATHETIC GANGLIA 89 



TABLE II 

 Possible bases of selective action 



1. Differences in factors of safety in nerve conduction and synaptic transmission. 



2. Non-uniform distribution of anesthetic due to differences in : 



Solubility 

 Permeability 

 Intracellular destruction 



3. Metabolic differences between nerve fibers and synaptic structures. 



other hand, urethane, whose effects are shown in the right-hand column of 

 Fig. 2, depressed pre- and postganglionic responses approximately equally, 

 thus lacking selective effect on the synapses in this preparation. Some other 

 anesthetics were found to be intermediate to the two used for illustrations, the 

 degree of selective action tending to increase with molecular weight among 

 the several agents tested (Larrabee and Posternak, 1952). 



In attempting to explain selective action, it is apparent that the well known 

 large factor of safety in nerve conduction as compared to synaptic transmission 

 may be of major importance (Table II). It is difficult, however, although per- 

 haps not impossible, to account on this basis for variations in intensity of se- 

 lective action exhibited by different substances at the same synapses (Larrabee 

 and Posternak, 1952). A second way of explaining selective action is to assume 

 that the agents appear at higher concentrations in critical synaptic structures, 

 such as the presynaptic endings or the postsynaptic cell body, than they do in 

 axons. This could result from localized differences in solubility, in permeability, 

 or possibly in rates of intracellular destruction of the anesthetic agent. A third 

 proposal for explaining selective action is based on a hypothetical difference 

 in the biochemistry of synaptic and axonal structures. For example, we might 

 suppose that particular enzymes affected by anesthetics are either less abun- 

 dant or more essential in certain synaptic parts of cells than they are in axons, 

 so that a given concentration of inhibitor could cause the greatest derangements 

 of cellular metabolism in synaptic regions. 



Metabolic theories of anesthetic mechanisms can explain selective action on 

 any of these several bases. In accordance with any such assumptions it seems 

 reasonable to suppose that selective effects might also be produced by meta- 

 bolic inhibitors other than anesthetics. Accordingly, we have tested the various 

 substances listed in Table III, chosen to represent a variety of metabolic sites 

 of action, as indicated in the last column (Larrabee and Bronk, 1952). For each 

 agent the concentration was determined at which the height of the preganglionic 

 response to supramaximal preganglionic stimulation was reduced to 80% of its 

 control value. At this concentration there always remained a sizable post- 

 ganglionic response, as indicated in the table, with the possible exception of a 



