Inhibitors okadaic acid

Surprisingly few studies have been performed with purified toxins. When added externally to the water, toxins of various origins were tested on the cope-pod Tigriopus californicus. The protein phosphatase inhibitor okadaic acid (17) from red tide dinoflagellates [22] and the neuronal depolarizing agent do-moic acid (10) from diatoms [40, 41] had different effects on the herbivores (Scheme 3). Micromolar concentrations of okadaic acid (17) acted both as toxin... 

The serine/threonine phosphatase inhibitor okadaic acid (incubation time and concentration vary from 10 nM, 30 minutes to 1 pM, 1 hour at 37°C) leads to selective stimulation of caveolae uptake (18,64). 

Chambers TC, Zheng B, Kuo JF (1992) Regulation by phorbol ester and protein kinase C inhibitors, and by a protein phosphatase inhibitor (okadaic acid) of P-glycoprotein phosphorylation and relationship to drug accumulation in multidrug-resistant human KB cells. Mol Pharmacol 41 1008-1015... 

Sakurada K, Zheng B, Kuo JF (1992) Comparative effects of protein phosphatase inhibitors (okadaic acid and calyculin A) on human leukemia HL60, HL60/ADR and K562 cells. Biochem Biophys Res Commun 187 488-492... 

J. B. J. Pietruszka, J. Total synthesis of the protein phosphatase inhibitor okadaic acid. 

Kauss, H. and Jeblick, W. 1991. Induced calcium uptake and callose synthesis in suspension-cultured cells of Catharanthus roseus are decreased by the protein phosphatase inhibitor okadaic acid. Physiol. Plant. 

Protein phosphatases inhibitors. Okadaic acid from marine dinoflagellates that accumulates in a black sponge (Halichondria okadal) and mussels, is a polyether fatty acid derivative. It causes a contracture of smooth and cardiac muscle, is a tumour promoter and selectively inhibits protein phosphatase-1 and phosphatase-2A. It is a causative agent in diarrhoretic shellfish poisoning. 

Depression of the force-RLC phosphorylation relation in intact smooth muscle was first described by Gerthoffer (1987), who demonstrated that elevating RLC phosphorylation by readdition of external Ca + in the presence of agonist was not accompanied by force development. Subsequently, others have shown depression of the force-RLC phosphorylation relation upon relaxation of activated smooth muscle with low concentrations of the phosphatase inhibitor okadaic acid or high external [Mg +] (Tansey et al., 1990 D Angelo etal., 1992, respectively, and Chapter 25, this volume). In these studies, relaxation was accompanied by... 

Armstrong et al. (1995) [4] showed that ABA induced anion efflux is independent of ABIl in tobacco. However, phosphorylation and dephosphorylation events are involved in control of anion efflux. Kinase antagonists or removal of ATP inhibits ABA induced slow anion channels in V faba guard cells suggesting that an ATP-dependent protein kinase is necessary for anion efflux. Down-regulation by removal of ATP can be reversed by the phosphatase inhibitor okadaic acid. Thus, the induction of slow anion channels by ABA is mediated by an ATP-dependent protein kinase and inhibited by a phosphatase. The phosphatase is distinct from ABIl which is not inhibited by okadaic acid [7], Furthermore,... 

Inhibition of MLCP appears to be a more general mechanism of increasing Ca +-sensitivity of contraction. The first experimental evidence that inhibition of MLCP can lead to an increase of Ca +-sensitivity was obtained with the phosphatase inhibitor, okadaic acid (Takai et al. 1987). Under more physiological conditions, MLCP is inhibited indirectly by a GTP dependent process (Kitazawa et al. 1991, Kubota et al. 1992) which may involve phosphorylation of the regulatory subunit of MLCP (Trinkle-Mulcahy et al. 1995). 

Boe, R. et al., The protein phosphatase inhibitor okadaic acid induces morphological changes typical of apoptosis in mammalian cells, Exp. Cell Res., 195, 231, 1991. 

Strnad, P, Windoffer, R., and Leube, R.E., In vivo detection of cytokeratin filament network breakdown in cells treated with the phosphatase inhibitor okadaic acid, Cell Tissue Res., 306, 211, 2001. 

Leira, F. et al., Apoptotic events induced by the phosphatase inhibitor okadaic acid in normal human lung fibroblasts, Toxicol. In Vitro, 15, 199, 2001. 

Messner, D.J. et ah. Abbreviated cell cycle progression induced by the serine/threonine protein phosphatase inhibitor okadaic acid at concentrations that promote neoplastic transofrmation. 

Corvera, S., Jaspers, S., and Pasceri, M., Acute inhibition of insulin-stimulated glucose transport by the phosphatase inhibitor, okadaic acid, J. Biol Chem., 266, 9271, 1991. 

Yessotoxin inhibited purihed protein phosphatase 2A with an EC50 of 0.36 mg/mL. This activity is lower than that of the classical protein phosphatase inhibitors (okadaic acid, dinophy-sistoxins) by four orders of magnitude [55], Unlike brevetoxins and ciguatoxins, yessotoxin and di-desulfoyessotoxin do not bind to the voltage-gated sodium channel of synaptosomal membranes from rat brain [62],... 

Das A Gale Jr M, Carter V et al. The protein phosphatase inhibitor okadaic acid induces defects in cytokinesis and organellar genome segr tion in Trypanosoma brucei. J Cell Sci 1994 107(Pt 12) 3477-83. 

Pouchus, Y.F., Dauvergne, S., Morel, D., Mondeguer, F., Marcaillou-Lebaut, C., Amzil, Z., and Verbist, J.F. (1998) Combined use of analytical high-performance liquid chromatography and cell morphology transformation assay to detect new protein phosphatase inhibitors okadaic acid type. Toxicon, 36, 383—389. 

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