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

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Abstract
Administration of iPr2P-F (di-isopropyl phosphorofluoridate) to rats produced a liver-dependent specific elevation of plasma .beta.-glucuronidase [EC 3.2.1.31] activity. The response was 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 iPr2P-F treatment, liver microsomal membranes were depleted of .beta.-glucuronidase but slowly returned to normal over 1 wk. Liver lysosomal .beta.-glucuronidase activity was high at early time points (< 60 min) after iPr2P-F administration but decreased to below control values; this lasted for a few days. The response to iPr2P-F was demonstrated in isolated hepatocytes prepared from iPr2P-F treated rats. In such preparations microsomal .beta.-glucuronidase was lost rapidly, followed by a specific decrease in hepatocyte lysosomal .beta.-glucuronidase. A pool of microsomal .beta.-glucuronidase may serve as precursor to plasma .beta.-glucuronidase in iPr2P-F treated rats, and microsomal .beta.-glucuronidase may serve as precursor to lysosomal .beta.-glucuronidase.