Effects of equinatoxin on the guinea-pig atrium.

Equinatoxin is a lethal protein isolated from a sea anemone, Actinia equina. The toxin (0.1-3 micrograms/ml) caused an initial inhibition followed by an augmentation of contractions and beating rates in the isolated guinea-pig atrium. The inhibitory phase was transient (30-60 sec), while the stimulant phase lasted for about 30 min. The treated atrium showed tachyphylaxis to the toxin. The inhibitory effect of the toxin was diminished by tetrodotoxin and atropine and abolished by 8-phenyltheophylline or mepacrine. Dipyridamole, which blocks the uptake of adenosine in the heart, enhanced the inhibitory effect. The stimulant effect of the toxin was inhibited by indomethacin or mepacrine and abolished by a combination of both, but was not inhibited by propranolol. Bioluminescent assay performed during the inhibitory phase showed an increased release of ATP and radioimmunoassay during the stimulant phase revealed an increased release of prostaglandin E2 from the treated atrium. These results suggest that the cardiac inhibitory effect of equinatoxin is mainly due to release of adenyl compounds, while the cardiac stimulant effect of the toxin may result from the liberation of arachidonic acid and subsequent formation of prostaglandins in the guinea-pig atrium.