SOME PHARMACOLOGIC PROPERTIES OF HOLOTHURIN, AN ACTIVE NEUROTOXIN FROM THE SEA CUCUMBER

¹ Naval Medical Research Institute, Bethesda, Md. (Friess and Standaert); National Institute of Neurological Diseases and Blindness, Bethesda, Md. (Whitcomb); Laboratory of Marine Biochemistry and Ecology, New York Zoological Society (Nigrelli); and Department of Chemistry, Mount Sinai Hospital, New York, N. Y. (Chanley and Sobotka)

The actions of the steroidal glycoside holothurin on amphibian nerve preparations and a mammalian nerve-muscle preparation have been studied. In general, the saponin has a powerful and irreversible action on both types of nerve, and appears to exert a direct, contractural effect on muscle.

Specifically, holothurin is comparable to the reference blocking agents cocaine, procaine and physostigmine in potency on desheathed bullfrog sciatic nerve. However, it affords a marked contrast with these reference agents in the sense that its action on this preparation is quite irreversible on washing, and it does not alter impulse conduction velocity in the course of its attenuation of the impulse. It displays the same irreversibility of action with respect to blockade of the action current in single fiber-single node nerve preparations from the toad and the frog.

On the rat phrenic nerve-diaphragm preparation, this material irreversibly blocks twitch response via either direct or indirect stimulation paths. Additionally, it displays a direct contractural effect on the muscle.