Purification of meprin from human kidney and its role in parathyroid hormone degradation.

Meprin (EC 3.4.24.18) is known to occur in the kidneys of mice and rats, but has not previously been found in human kidneys. Here we report the isolation of meprin from human kidney and show that it has a role in the degradation of parathyroid hormone (PTH) in that organ. The purified human meprin had properties almost identical to those of rat meprin including molecular size, substrate specificity and inhibitor sensitivity, and it also cross-reacted well with an antibody raised against rat meprin. Both the purified human meprin and the microvillar membranes of human kidney readily hydrolyzed human parathyroid hormone [hPTH-(1-84)] into several fragments, whose amino acid sequences corresponded well to each other. Thus, meprin appears to play a major role in the PTH-degrading activity in the microvillar membranes of human kidney. Our results indicate that meprin, which so far has mainly been investigated in mice and rats, is found not only in these rodents, but also in the human kidney, and suggest that its physiological role in humans is to degrade PTH in the kidney.