LATENCY IS THE MAJOR DETERMINANT OF UDP-GLUCURONOSYLTRANSFERASE ACTIVITY IN ISOLATED HEPATOCYTES

The glucuronidation of p-nitrophenol was measured in intact, saponin- and alamethicin-treated isolated mouse hepatocytes. In saponin-permeab ilized cells the elevation of extrareticular UDP-glucuronic acid conce ntration enhanced the rate of glucuronidation threefold. When intracel lular membranes were also permeabilized by alamethicin, a further tenf old increase in the glucuronidation of p-nitrophenol was present. Para llel measurements of the ER mannose 6-phosphatase activity revealed th at saponin selectively permeabilized the plasma membrane, whereas alam ethicin permeabilized both plasma membrane and ER membranes. The inhib ition of p-nitrophenol glucuronidation by dbcAM P in intact hepatocyte s was still present in saponin-treated cells and disappeared in alamet hicin-permeabilized hepatocytes. It is suggested that the permeability of the endoplasmic reticulum membrane is a major determinant of glucu ronidation not only in microsomes but in isolated hepatocytes as well.