Marine Toxins Origin, Structure, and Molecular Pharmacology

摘要

Red tides resulting from blooms of the dinoflagellate Ptychodiscus brevis in theGulf of Mexico have elicited a great deal of scientific interest since the first documented event over 100 years ago (1). Human intoxications from the ingestion of contaminated shellfish and the impact of massive fish kills on the tourist industry along the Gulf coast of the United States have resulted in a concerted research effort to understand the genesis of red tides and to isolate and characterize the toxins of P. brevis. Methods of detection, metabolism, and pathophysiology of the brevetoxins, PbTx-2 and PbTx-3, are summarized. Infrared spectroscopy and innovative chromatographic techniques were examined as methods for detection and structural analysis. Toxicokinetic and metabolic studies for in vivo and in vitro systems demonstrated hepatic metabolism and biliary excretion. An in vivo model of brevetoxin intoxication was developed in conscious tethered rats. Intravenous administration of toxin resulted in a precipitous decrease in body temperature and respiratory rate, as well as signs suggesting central nervous system involvement. A polyclonal antiserum against the brevetoxin polyether backbone was prepared; a radioimmunoassay was developed with a sub-nanogram detection limit. This antiserum, when administered prophylactically, protected rats against the toxic effects of brevetoxin.