PHYSIOLOGY AND BIOCHEMISTRY OF SHOCK 421 



ATP does not affect the strength-duration curve of a muscle. In 

 denervated muscle intra-arterial injection of acetylcholine renders the 

 muscle insensitive to subsequent application of ATP, and prevents the 

 release of contraction by ATP (Buchthal, et al, 1946, 1948). 



ATP applied to muscle increases its sensitivity towards intra-arterially 

 injected acetylcholine four to ten-fold. Inorganic triphosphate has a 

 similar effect. The effect is not on the neuromuscular transmission 

 but on the muscular substance, since it is elicited also in curarized 

 muscle. Why small amounts of acetylcholine prevent ATP adminis- 

 tered through the artery from producing a response is not clear. Large 

 amounts also inhibit the release of contraction by intramuscularly 

 applied ATP. Since, however, the electrical excitability was retained, 

 it was assumed that acetylcholine somehow prevents a contact between 

 ATP and the contractile muscle elements (Buchthal and Folkow, 

 1948). 



g. Role of Acetylcholine in Anaphylactic Shock. A consideration 

 of the above presented data shows clearly the various effects acetyl- 

 choline is able to exercise. It is obvious that a certain concentration 

 of endogenous acetylcholine must be built up for a measurable effect. 

 The question of whether or not a physiologically significant concentra- 

 tion of this substance can be built up at the site of "shock organs" must 

 be considered. The high activity of choline esterase in destroying the 

 liberated acetylcholine must form part of our consideration. Apparently 

 there are other esterases, besides choline esterase, which destroy 

 acetylcholine. It is reported that 10iu,g of acetylcholine incubated for 

 one hour with dog serum plus a minute amount of eserine, when in- 

 jected into a cat, manifests the characteristic vasodepressor action; with- 

 out eserine this action was not observed. On the other hand, the 

 analogues of acetylcholine which are resistant to the hydrolytic action of 

 serum esterases, in the absence of eserine, are found to elicit a fall in 

 blood pressure. Carbaminocholine, (CH3)3N(OH)-CH2CH20- 

 CONH2, and acetyM-methylcholine, CCH3)3N(OH)CH2CH2- 

 (CH3)OCOCH3, are of these types. The latter compound is approxi- 

 mately 200 times more potent than acetylcholine, (CH3)3^N (OH)- 

 CH2CH2OCOCH3, in evoking cardiovascular responses in man. 

 Choline, though 500 to 100,000 times less potent, resembles acetyl- 

 choline in acting as vasodepressor agent (Goodman and Gilman, 

 1941). 



