EFFECTS ON TISSUE FUNCTIONS 499 



obtained with iodoacetate, as did Lecomte and Fischer (1948), who found 

 that both p-benzoquinone and 2,6-dimethoxy-p-benzoquinone at 0.092 mM 

 cause a slow irreversible contracture of the frog rectus abdominis muscle. 

 It is interesting, but unexplained, that 2-hydroxy-l,4-naphthoquinone 

 causes a reversible contracture. No studies of the metabolic changes as- 

 sociated with the actions of the quinones on intact muscle have been made, 

 but several workers have noted that the respiration of muscle, more than 

 most tissues, is often stimulated by both benzo- and naphthoquinones. One 

 must also consider the possibility that at least part of the action is by hy- 

 drogen peroxide formed in the reoxidation of the hydroquinones, this 

 leading to a glycolytic block. 



The neuromuscular junction appears to be fairly sensitive to the quinones, 

 which was indicated in the early work of Labes (1929 a) who found the 

 indirect excitability through nerve stimulation to fail much earlier than 

 direct excitability of the muscle during exposure to p-benzohydroquinone 

 aerobically. The twitches are abolished by treatment of the muscle with 

 curare or increasing the Ca++ concentration 4- to 6-fold (Sterin, 1935), in- 

 dicating that the effect is related to chohnergic mechanisms at the end- 

 plate. Hydroquinones are able to stimulate contractions in certain nerve- 

 muscle preparations. Thus Sterin (1938) found ^^-benzohydroquinone to 

 augment contractions in frog muscle fatigued by stimulation through its 

 nerve, and Tagaki (1939) found both p-benzohydroquinone and catechol 

 at low concentrations (0.002-0.009 mM) to increase the contractions of 

 toad gastrocnemius stimulated through the sciatic nerve. Indeed, these 

 hydroquinones have the ability to antagonize the neuromuscular block by 

 curare, as shown by Mogey and Young (1949) in the rat phrenic nerve- 

 diaphragm preparation. Such an action is most readily interpreted by an 

 inhibition of cholinesterase, but they found brain and serum cholinesterase 

 to be inhibited very weakly by both p-benzohydroquinone and catechol. 

 Reaction with tubocurarine is unlikely, so the mechanism was unexplained. 

 An inhibition of cholinesterase cannot be eliminated because, first, muscle 

 cholinesterase was not tested and, second, inhibition by hydroquinones 

 might occur more readily in the intact muscle due to higher levels of the 

 corresponding quinone. Torda and Wolff (1946 a) indeed found p-benzo- 

 hydroquinone to increase the response of frog muscle to acetylcholine, while 

 simultaneously there is a decreased contraction from K+, pointing to an 

 inhibition of cholinesterase or some unknown action on the acethylcholine 

 receptors. It is unfortunate that the actions of p-benzoquinone were not 

 examined in any of this work. 



Actually one might expect acetylcholine synthesis to be more easily 

 inhibitable than cholinesterase by the quinones; this seems to be true from 

 the work of Torda and Wolff (1945) on frog brain, in which the synthesis is 

 inhibited by jj-benzohydroquinone at concentrations above 0.01 mM. 



