Origin of urinary alkaline phosphatase excreted by cadmium-treatment of rabbits

In order to ascertain the origin of increased alkaline phosphatase in the urine of rabbits with injured proximal tubules, we studied the phosphatase by an isoenzyme examination, an inhibition test and an inactivation test. Male rabbits were daily injected subcutaneously with cadmium chloride at a dose of 1.5 mg Cd/kg/day. After treatment for three weeks, total activity of alkaline phosphatase and its isoenzyme patterns on agar-gel and disc-gel electrophoresis were examined in the liver, kidney cortex, plasma and urine, and compared with those of the control rabbits. Alkaline phosphatase activity in the urine of the cadmium treated rabbit was about eleven times higher than that of the control (p = less than 0.005), while enzyme activity of plasma showed almost no difference between the two groups. The isoenzyme patterns of alkaline phosphatase in both agar-gel and disc-gel electrophoresis showed that the main band of the isoenzymes of alkaline phosphatase obtained from urine of control rabbits migrated faster than that from plasma, liver, or kidney, while the main isoenzyme from urine of the cadmium group was consistent with the rapid migrating isoenzyme obtained from the kidney. Furthermore, in both groups, alkaline phosphatase activity in plasma was inactivated by the treatments of heat and urea, and inhibited by L-homoarginine, while the enzymes of the kidney and urine were not remarkably effected. The findings suggest that the increased urinary excretion of the enzyme after administration of cadmium to rabbits originates from the kidney.