Effects of di-isopropyl phosphorofluoridate on rat liver microsomal and lysosomal beta-glucuronidase

Abstract

iPr(2)P-F (di-isopropyl phosphorofluoridate) administration to rats produces a liver-dependent specific elevation of plasma beta-glucuronidase activity. The response is unaffected by puromycin pretreatment. By using subcellular-fractionation techniques, the rise in plasma beta-glucuronidase activity was correlated temporally with a fall in liver microsomal beta-glucuronidase activity. After iPr(2)P-F treatment, liver microsomal membranes are depleted of beta-glucuronidase but slowly return to normal over 1 week. On the other hand, liver lysosomal beta-glucuronidase activity is high at early time points (less than 60min) after iPr(2)P-F administration but decreases to below control values; this lasts for a few days. The response to iPr(2)P-F was demonstrated in isolated hepatocytes prepared from iPr(2)P-F-treated rats. In such preparations, microsomal beta-glucuronidase is lost rapidly, followed by a specific decrease in hepatocyte lysosomal beta-glucuronidase. The results suggest that a pool of microsomal beta-glucuronidase serves as precursor to plasma beta-glucuronidase in iPr(2)P-F-treated rats, and further, that microsomal beta-glucuronidase may serve as precursor to lysosomal beta-glucuronidase.