Aspects of the spasmogenic effects of acetate esters on ileal smooth muscle.

Acetate esters, such as aspirin methylester, aspirin and resorcinol monoacetate, induced contractions of guinea-pig ileum. Their actions were selectively antagonized by atropine, but were not affected by ganglion blocking agents, conduction blockers, aging with cooling, anoxia or antihistaminics. On the other hand, N-acetates, such as acetanilide and p-acetaminophenol, and no contractile action on the ileum. These acetate esters thus seemed to have a cholinergic action, and not a direct action on muscle or other known specific receptors for endogenous active substances. The contractions induced by the acetate esters were selectively potentiated by low concentrations of choline, whereas those induced by acetylcholine, nicotine, 5-hydroxytryptamine and histamine were not. However, N-acetates did not induce the contractions even in the presence of choline. Organophosphorus cholinesterase inhibitors, such as diisopropyl fluorophosphate and paraoxon, selectively and irreversibly inhibited the actions of aspirin and N,O-diacetyl-p-aminophenol with or without choline. From these results, it is concluded that the acetate esters with or without choline act through the cholinergic system. However, their actions cannot be explained in terms of known mechanisms, such as acetylcholine release, cholinesterase inhibition or a direct muscarinic action. Therefore, the acetate esters, including phenyl acetate which was supposed to be a releaser of acetylcholine, seem to have a hitherto undescribed type of cholinergic action whose mechanism is unknown. It seems that organophosphate-sensitive esterase(s) in the preparation may be essential for initiation of the actions of the acetate esters with or without choline, but the mechanism of the effect of choline is unknown.