Serum calcium-decreasing factor (caldecrin) from porcine pancreas has proteolytic activity which has no clear connection with the calcium decrease

Abstract

We purified a serum calcium-decreasing factor, which showed chymotrypsin-like protease activity, from porcine pancreas to homogeneity. The factor administered to mice intravenously at a dose of 20 micrograms/kg b.w. decreased serum calcium by 15%. Treatment of the factor with the serine protease inhibitor, PMSF, caused a leftward shift in the dose-response curve, showing strengthened activity. It also caused a decrease in serum calcium and hydroxyproline levels in rats. At a dose of 10 ng/ml, the factor inhibited 45Ca release from cultured fetal long bone stimulated by parathyroid hormone (PTH) and PTH-related protein, but not by interleukin-1 alpha, prostaglandin E1 and 1,25-dihydroxy vitamin D3. No other well-known pancreatic proteases had these effects. In view of the results of experiments using protease inhibitor and pancreatic proteases, and in view of the specificity of this factor in vitro, we propose that the factor exerts its serum calcium-decreasing activity most probably not through proteolytic degradation of PTH, but through an inhibition of PTH action on bones by a yet undefined mechanism.