Effect of 4-aminopyrazolo[3,4-d]pyrimidine on the catabolism of high-density lipoprotein apolipoprotein A-I in the rat.

The in vivo turnover and sites of catabolism of O-(4-diazo-3-[125I]iodobenzoyl)sucrose-labelled rat high-density lipoprotein (HDL) apolipoprotein A-I were studied in rats treated for 3 days with 4-aminopyrazolo-[3,4-d]pyrimidine (4APP). It was found that 4APP treatment decreases the serum cholesterol concentration to 6 mg/dl and stimulates the serum decay of labelled HDL. The latter effect could be attributed to an increased catabolism of radioactive HDL apolipoprotein A-I by the liver. When the serum cholesterol concentration was raised to physiological levels by a bolus injection of unlabelled rat HDL, at the time of administration of the labelled HDL, the serum decays and the tissue uptakes of apolipoprotein A-I labelled HDL were identical in 4APP-treated rats and control animals. When a bolus injection of unlabelled human low-density lipoprotein (LDL) was administered to 4APP-treated rats, the serum decay and tissue uptake of apolipoprotein A-I labelled HDL remained rapid. The recovery of radioactivity in the adrenal glands was increased almost 10 fold by 4APP treatment, a phenomenon which was reversed by a bolus injection of unlabelled HDL, but not by injection of unlabelled LDL. It is concluded that treatment of rats with 4APP does not affect the rate of catabolism of rat HDL apolipoprotein A-I, when the serum HDL concentration in the treated animals is restored to physiological levels.