Effect of ethacrynic acid on guinea pig ileum

The effect of ethacrynic acid on the motor function of guinea pig ileum was studied in vitro. Ethacrynic acid produced dose-related (5-160 microgram/ml) contractions in this tissue. Morphine, tetrodotoxin and sodium-free medium prevented the contractions while hexamethonium, diphenhydramine, methysergide or indomethacin did not. Atropine in a high concentration (0.1 microgram/ml) only inhibited the contractions. Ethacrynic acid inhibited the contraction of ileum induced by electrical stimulation of intramural nerves. This was not prevented by pretreatment with reserpine. Repeated exposure to ethyacrynic acid developed tachyphylaxis in contractile response. Inhibition of electrically elicited contraction of guinea pig ileum also diminished with repeated treatment. Ethacrynic acid (80-160 micrograms/ml) inhibited the peristaltic reflex of the guinea pig ileum. It is concluded that the excitatory effect of ethacrynic acid is most probably mediated by the release of neurotransmitter, however, the mechanism of the inhibitory effect remains to be elucidated.