On the relation between peripheral cleavage of parathyroid hormone and its biological activity in kidney

Abstract

The time course of the renal metabolism of electrolytically iodinated 125I-bPTH(1–84) (E-PTH), previously shown to retain biological activity, was compared with that of Chloramine-T labeled, biologically inactive 125I-bPTH(1–84) (CT-PTH), the assumption being that observed differences would reflect biological specificities of metabolism. Denaturant gel filtration of kidney extracts indicated that the initial rate of cleavage of E-PTH was more rapid than that of CT-PTH. This difference was maximal at 5 minutes when the amount of unmetabolized hormone, expressed as a percentage of total kidney radioactivity was 40% for E-PTH and 68% for CT-PTH. The time courses of disappearance of intact E-PTH and CT-PTH from serum were similar. The metabolism of PTH labeled by the two methods was studied in vitro in rat renal cortical plasma membranes (RCPM). As was the case in vivo, E-PTH was cleaved 2–3 times more rapidly than CT-PTH by RCPM. Basal lateral membranes, containing PTH responsive adenylate cyclase activity, and brush border membrane fractions separated by free flow electrophorosis of RCPM also metabolized E-PTH 2–3 times more rapidly than CT-PTH. E-PTH metabolism in RCPM was not inhibited by 10 −6 M unlabeled bPTH(1–84). However, histone f 3 (1mg/ml) completely blocked metabolism of E-PTH in RCPM, and enhanced PTH-stimulated adenylate cyclase activity 5 fold