Cooliatoxin, the first toxin from Coolia monotis (Dinophyceae).

Abstract

Coolia monotis is a benthic dinoflagellate previously thought to be non-toxic. We describe a new toxin, named cooliatoxin, purified from cultures of a strain of C. monotis isolated from Australia. Cooliatoxin is likely a mono-sulphated, polyether toxin (M = 1,062; i.p. LD50 = 1 mg/kg in mice) that induces hypothermia and respiratory failure in mice after a pronounced delay period during which there are no obvious signs of intoxication. These signs in mice are similar to those reported for the shellfish toxin named yessotoxin and the molecular weight of cooliatoxin corresponds to the mono-sulphated form of yessotoxin, suggesting that cooliatoxin may be an analogue of yessotoxin. Cooliatoxin has no effect on the mouse phrenic nerve or diaphragm musculature in vitro but causes initial stimulation and subsequent block of unmylenated nerves in vitro. In isolated guinea pig left atria, cooliatoxin (above 20 nm) induced a slow developing concentration dependent sustained inotropic response. Propranolol or tetrodotoxin reversed the positive inotropic effects, indicating that the majority of the cooliatoxin induced response was mediated by stimulation of nerves associated with the atrial musculature, resulting in the release of noradrenaline. Cooliatoxin induced transient contractions in isolated guinea pig vas deferens preparations. Atria and vas deferens preparations were tachyphylactic to a second equivalent dose of cooliatoxin applied after the effects of the first dose had diminished. The observed in vitro effects of cooliatoxin on peripheral nerves are unlikely to account for the lethal effects in mice and a central action of this toxin is suspected.