CELLULAR-DISTRIBUTION OF EXOGENOUS APROTININ IN THE RAT-KIDNEY

Aprotinin, an inhibitor of the enzymatic activity of kallikrein in vit ro, has been used to study the possible contributions of the kallikrei n-kinin systems to physiological and pathological conditions. Pharmaco kinetic studies indicate that aprotinin is concentrated in the kidney; however, there is little information with regard to its cellular dist ribution. The purpose of the present work was to study the cellular di stribution of aprotinin, which would be valuable for a better understa nding of its intrarenal effects. Sprague-Dawley rats (200-250 g, n = 3 6) received aprotinin (50 000 KIU/rat) and were killed at different in tervals after its administration. The kidneys were examined histologic ally and the cellular distribution of aprotinin was studied by immunoh istochemistry. Aprotinin was localized at 30 min concentrated within v esicles in the apical border of the proximal tubule cells. Later (2 h) it was observed distributed over the cytoplasm, where it remained for the 24 h studied. Aprotinin was also detected in connecting tubule ce lls colocalized with kallikrein, and in the basal portion of collectin g tubule cells. No evidence of endogenous aprotinin was observed. The binding of aprotinin to the connecting tubule cells and collecting duc ts offers a partial explanation of its renal effects.