INHIBITION OF MICROSOMAL CHOLESTEROL ESTER HYDROLASE BY OKADAIC ACID IN ISOLATED RAT HEPATOCYTES

Okadaic acid, a potent and specific inhibitor of protein phosphatases 1 (IC50 10-20 nM) and 2A (IC50 0.05-2 nM) caused early and sustained i nhibitions of microsomal cholesterol ester hydrolase activity in hepat ocyte suspensions. The changes in the kinetic properties of the estera se and its response to exogenous alkaline phosphatase and cyclic AMP-d ependent protein kinase after cell exposure to 1 mu M or 1 nM okadaic acid differed markedly among themselves, which suggests the involvemen t of both protein phosphatases 1 and 2A in the regulation of the micro somal hydrolysis of cholesterol esters. Furthermore, the inhibitory ef fect of okadaic acid is likely to be independent of the dibutyryl-cycl ic AMP promoted cell events leading to stimulation of esterase activit y.