SPECIFIC PRORENIN RENIN BINDING (PROBP) - IDENTIFICATION AND CHARACTERIZATION OF A NOVEL MEMBRANE SITE/

Renin can be detected in cardiovascular and other tissues but it disap pears after bilateral nephrectomy indicating that tissues can take up or bind renal renin from the circulation. If renin uptake is the resul t of specific binding, plasma prorenin may be a natural antagonist of tissue directed renin-angiotensin systems. To investigate if specific prorenin/renin uptake occurs in rat tissues, binding studies were perf ormed with rat microsomal membrane preparations using recombinant rat prorenin metabolically labeled with S-35-methionine as a probe. A high affinity binding site for both renin and prorenin was identified. Aff inities for prorenin and renin were approximately 200 and 900 pmol/L, respectively. Binding was reversible, saturable, and pH and temperatur e dependent. The relative binding capacities of membranes from various rat tissues were as follows (fmol/mg): renal cortex (55), liver (54), testis (63), lung (31), brain (18), renal medulla (15), adrenal(17), aorta (7), heart (4), and skeletal muscle (1). Bound prorenin was disp laced by rat and human renin or prorenin but not by the prosequence of rat prorenin, angiotensin I or II, rat or human angiotensinogen, the renin inhibitor SQ30697, atrial natriuretic factor, amylase, insulin, bovine serum albumin, hemoglobin, heparin, lysozyme, ovalbumin, cytoch rome C, pepsin, pepsinogen, ribonuclease A, mannose-6-phosphate, alpha -methyl mannoside, gonadotropin releasing hormone, or an antibody to h og renin binding protein. These results demonstrate specific binding o f prorenin to a site in rat tissues, herein named ProBP, that also bin ds renin. It is possible that differences in prorenin/renin binding ca pacity determine the activity of tissue-directed renin-angiotensin sys tems and that prorenin is a natural antagonist. Alternatively, a prore nin/renin receptor may have been identified that may function by trans ducing an intracellular signal.