Neuromuscular and cytotoxic effects of holothurin A and related saponins at low concentration levels. III

Abstract

Further studies have revealed new parameters attending the toxic interactions of holothurin A with a variety of nerve and neuromuscular preparations. In particular, low concentrations of this saponin-like agent produce tissue responses that are largely irreversible. On the viable single fiber preparation from frog sciatic nerve, 10 μg of the agent per milliliter causes irreversible loss of nodal excitability and concomitant loss of basophilic, macromolecular material from the axoplasm in and near the node of Ranvier. In contrast, 2 μg of this agent per milliliter blocks conduction along the fiber but does not produce consistent morphologic changes at and near the nodes and does not destroy electrical excitabilty of a given isolated node. Related phenomena have also been observed with Quillaja saponin and with digitonin. On the rat phrenic nerve-diaphragm preparation, a 1 × 10 −4 M level of holothurin produces irreversible knockout of both directly and indirectly elicited twitch responses, as previously noted. But, preconditioning of the preparation with tiny concentrations of physostigmine (in the 10 −10 to 10 −9 M range) prevents this irreversible destruction of twitch response. Yet, in the case of the twitch elicited via nerve stimulus, the protection afforded by physostigmine vanishes at concentrations in excess of 7 × 10 −9 M. These results are discussed in terms of possible modes of interaction of this animal saponin with chemoreceptors in nerve and neuromuscular tissues.