Palytoxin: membrane mechanisms of action.
Palytoxin is a marine toxin originally isolated from the zoantharians of the genus Palythoa, but now is found in marine organisms ranging from dinoflagellates to fishes. With a MW of 2680, it is one of the largest nonpolymeric natural products ever found. Its complex structure has been elucidated and total synthesis has been achieved. With an LD(50) of 25 ng/kg for rabbits (the most sensitive species), it is one of the most lethal marine toxins. It binds to the Na,K-ATPase specifically with a K(D) of 20 pM. It has a unique action on the Na,K-ATPase, converting the pump into an ion channel and resulting in K(+) efflux, Na(+) influx and membrane depolarization. As a result palytoxin causes a wide spectrum of secondary pharmacological actions. By acting like a key to unlock the internal structure of the Na,K-ATPase, palytoxin holds promise as a useful tool for investigation of the pump molecule.
Wu
Chau H
CH
Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611-3008, USA. chauwu@sbcglobal.net
D000178:Acrylamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D003064:Cnidarian Venoms; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008387:Marine Toxins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D023382:Toxicity Tests, Acute; D000095702:Polyether Toxins
D000178:Acrylamides; D003064:Cnidarian Venoms; D007473:Ion Channels; D008387:Marine Toxins; D000254:Sodium-Potassium-Exchanging ATPase; C010272:palytoxin; D000095702:Polyether Toxins