Specific renin/prorenin binding: prorenin as a potential antagonist of tissue-directed renin.

The purpose of this study was to investigate if specific renin/prorenin uptake occurs in rat tissues. Binding studies were performed with rat microsomal membranes using metabolically labeled 35S methionine recombinant rat prorenin as a probe. A high affinity binding site for both prorenin and renin was identified with affinities of approximately 200 and 900 pMolar respectively. Binding was reversible, saturable, pH and temperature dependent. Binding capacities to rat tissues were (fmol/mg): renal cortex (55), testis (63), lung (31), brain (18), renal medulla (15), adrenal (17), aorta (7), heart (4) and skeletal muscle (1). Bound prorenin was displaced by rat and human renin or prorenin but not by: rat prorenin prosequence, Ang I or II, angiotensinogen, the renin inhibitor SQ30697, ANF, amylase, insulin, bovine serum albumin, hemoglobin, heparin, lysozyme, ovalbumin, cytochrome C, pepsin, pepsinogen, ribonuclease A, mannose-6-phosphate, alpha methyl mannoslde, GnRH or an antibody to hog renin binding protein. These studies have identified a specific binding site for renin in rat tissues that also binds prorenin. Binding capacity differs between tissues indicating that changes in binding could determine the activity of tissue-associated renin systems. Since it competes for binding, prorenin may be a natural antagonist of tissue-directed renin-angiotensin systems.