Mechanism of Inactivationin Vitroof Parathyroid Hormone by Rat Kidney Slices

Abstract

The influence of Ca++, Mg++, cysteine, 2,4-dinitrophenol, a trypsin inhibitor (Trasylol) and an antiplasmin drug (epsilon-aminocaproic acid) on the inactivation of parathyroid extract (PTH) was studied, using aerobic incubation with rat kidney slices in Robinson''s bufferp, H 7.4, at 37 C for 1 hr, followed by use of the Munson assay for calcium-mobilizing activity. Calcium ions in a concentration of 12.5 mM/1, the trypsin inhibitor and epsilon-aminocaproic acid markedly inhibited the inactivation of para-thyroid hormone by rat kidney slices, while 11.0 m[image]/l of magnesium ions, cysteine and 2,4-dinitrophenol had no such effect. The incubation medium itself, obtained after preincubation with rat kidney slices, scarcely inactivated the PTH activity, indicating that the site of in-activation was within the slices. Kidney slices obtained from rats injected with 3.0 g/kg of sodium tartrate subcutaneously were devoid of PTH-inactivating ability, while those obtained from animals to which 0.05% HgCl2 was given by retrograde infusion throught the ureter displayed an inactivating ability similar to that of intact animals. These results suggest that proteolytic enzymes in rat kidney tissue may play a role in the inactivation of parathyroid hormone.