Proteolysis of Parathyroid Hormone in Vitro by Sera from Acute Pancreatitis Patients 1

Abstract

The degradation of ¹²⁵I-labeled parathyroid hormone in vitro has been investigated in order to test the hypothesis that proteolytic degradation of PTH may be related to the hypocalcemia associated with acute pancreatitis. A polyacrylamide gel electrophoresis technique has been employed to separate bovine PTH (1-84) from lower molecular weight peptides produced by proteolytic cleavage. It has been demonstrated that trypsin bound to the plasma protease inhibitor α₂-macroglobulin rapidly degrades PTH and destroys its biological activity in vitro in a kidney cortex adenyl cyclase assay system. Substantial PTH degrading activity was also detected in serum samples obtained from nine patients with severe acute pancreatitis. In contrast, significant PTH degradation could not be detected in normal serum or plasma. Furthermore, no degradation was observed with sera from two patients with mild pancreatitis due to biliary tract stones or four patients with hyperamylasemia but no evidence of pancreatic disease. The PTH degrading activity in patient sera could be blocked by the combination of two peptide chloromethylketones that specifically inhibit the pancreatic endopeptidases trypsin, chymotrypsin, and elastase 2. These results suggest that the FTH degradation assay represents a sensitive test for biologically relevant proteolytic activity in acute pancreatitis, and that it can specifically detect molecular forms of the pancreatic proteases in blood reflecting the intrapancreatic activation of zymogens in the course of pancreatic inflammation.