IMMUNOCYTOCHEMICAL LOCALIZATION OF PROANF-1-30, PROANF-31-67, ATRIAL-NATRIURETIC-FACTOR AND URODILATIN IN THE HUMAN KIDNEY

Whether ProANF 1-30 [first 30 amino acids (a.a.) of the 126-a.a. atria l natriuretic factor (ANF) prohormone] and ProANF 31-67 (a.a. 31-67 of this prohormone) with their natriuretic and diuretic properties are p resent within the human kidney is unknown. In the present investigatio n, ProANFs 1-30 and 31-67 as well as ANF (a.a. 99-126) of the ANF proh ormone localized to the subbrush border of the pars convoluta and pars recta of the proximal tubules of the human kidney with immunoperoxida se staining. Immunofluorescent studies revealed that each of these pep tides had a strong inclination for the perinuclear region in the proxi mal and distal tubules. ProANFs 1-30, 31-67 and 99-126 (i.e. ANF) also localized with both immunoperoxidase and immunofluorescent staining t o the cortical collecting ducts, glomeruli, and peritubular and inters titial blood vessels. ANF immunoperoxidase staining was particularly s triking in the endothelium of interstitial arteries and vasa recta. In the glomeruli, prominent staining was noted in the peripheral glomeru lar capillary wall and in some of the visceral epithelial cells. In co ntrast, urodilatin (i.e. a.a. 95-126 of the ANF prohormone) was not fo und in the proximal tubules, but weak staining was found in the distal tubules and interstitial vessels with some but not all glomeruli, per itubular vessels, cortical collecting tubules and outer medullary neph rons weakly staining by immunoperoxidase and immunofluorescent methods . The whole prohormone being present in the kidney was suggested by im munological recognition of both the N- and C-termini of the ANF prohor mone by radioimmunoassays. The concentration of the N-terminus in the kidney was 1.6 +/- 0.03 ng/g of kidney weight, while the C-terminus of the ANF prohormone concentration was 1.2 +/- 0.3 ng/g of kidney tissu e. These findings of a sub-brush border and perinuclear location of th e N- and C-terminal ANF prohormone peptides suggest that the ANF proho rmone may be synthesized in and/or the respective peptides are capture d by the proximal tubules but also to a lesser extent by the distal tu bules of the kidney. Urodilatin formation appears to be in the distal nephron.