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Free keywords:
Renal Transport; Transport of Protein; Pinocytosis; Lysosomal Digestion; Protease Inhibitor
Abstract:
The bovine protease inhibitor aprotinin (Trasylol®) has a high affinity to the kidney and is preferentially pinocytized in the proximal tubule. After i.v. injection of 1mug 124I aprotinin the blood content decreases to 2.8% of the primary injected amount within 3 hrs, while simultaneously each kidney contains 29%. This substance was used to test whether or not a peptide which is pinocytized, is released in the intact form into the peritubular blood. By a cross circulation technique with two unilaterally nephrectomized rats we were unable to detect any transport of pinocytized, intact peptide through the proximal tubule cell over the observed cross circulation period of 1-8 hrs even when using 5000 times the above dosage. Since the total amount of aprotinin in the kidney is immunologically reactive (ca. 97%), and 65% of the radioactivity in the blood is not reactive after 6 hrs, we believe that the last step in the absorption process consists in digestion inside the lysosomes and instantaneous release of the split products into the blood.
