neuronal mechanisms releasing neurotransmitters, because antagonists of adrenalin, acetylcholine, histamine and 5-hydroxytryptamine (5HT) did not affect the response to okadaic acid r. Smooth muscle contraction is triggered by the phosphorylation of one of the small subunits of myosin, the P-light chain, suggesting that okadaic acid might activate myosin P-light chain kinase or inhibit a myosin P-light chain phosphatase. Takai and co-workers established that the latter idea was correct and went on to show 9 that okadaic acid is a very potent inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), two of the four major protein phosphatases in the cytosol of mammalian cells that dephosphorylate serine and threonine residues (reviewed in Refs 10, 11). These, and subsequent studies~ 2, 1:, have established that okadaic acid is a specific inhibitor of PP1 and PP2A, which are structurally related enzymes showing 50% amino acid sequence identity in the catalytic domain ml. Of the other two major protein-serine/threonine phosphatases, the Ca'-'+/calmodulindependent protein phosphatase 2B (PP2B) is far less sensitive, while the Mg2+-dependent protein phosphatase 2C (PP2C) is unaffected. The mitochondrial pyruvate dehydrogenase phosphatase 2, protein phosphatases that dephosphorylate tyrosine residues, acid and alkaline phosphatases~, and inositol trisphosphatas&, are also insensitive to the toxin, nor is there any inhibition of eight different protein kinases that have been tested, such as cyclic AMP or Ca>/calmodulindependent protein kinases, or protein kinase C J2':~.