[40] Use of okadaic acid to inhibit protein phosphatases in intact cells

Okadaic acid is a marine toxin originally isolated from the black sponge, Halichondria okadaii. It is now known to be one of a family of related toxins, including dinophysistoxin 1 and acanthifolicin. These toxins are synthesized by dinoflagellates, especially of the genus Dinophysis, but the toxins accumulate in organisms further up the food chain, including sponges, shellfish, and, ultimately, humans. In humans, consumption of contaminated shellfish causes diarrhetic shellfish poisoning, and this is a particular problem at certain times of year when there is a proliferation of plankton containing the dinoflagellates. Okadaic acid is a complex fatty acid derivative containing numerous polyether linkages. It is an extremely valuable tool for testing the physiological role of protein phosphorylation in any physiological response in intact cells. It has been shown to act as a tumor promoter in the mouse skin bioassay, but unlike many other tumor promoters does not activate protein kinase C. The structure of okadaic acid is very hydrophobic, which makes it possible to be used it as a protein phosphatase inhibitor in intact cells.