In vivo interaction of the Kunitz protease inhibitor and of insulin with subcellular structures from rat renal cortex.

Rats were injected with labeled Kunitz protease inhibitor and killed at various times thereafter. Radioactivity was measured in various fractions of kidney homogenates in order to study the time-dependent fixation to different cell organelles, expecially the transition from the brush border to lysosome fraction. With short survival periods (up to 5 min), the renal protease inhibitor is recovered nearly completely with the brush border fraction. With longer periods, a shift towards particles with higher densities and higher beta-glucuronidase activities takes place. Similar results have been achieved with insulin. Lysosomes were prepared and subfractionated following i. v. administration of the protease inhibitor or insulin. The radioactivity of the peptides was found in the lysosomal range of density. According to our present and previous results, the renal pathway of the protease inhibitor consists of 3 steps: binding to the brush border, reabsorption into micropinocytotic vesicles and phagosomes, and final enrichment in phagolysosomes with subsequent degradation. We suggest this type of transport to be representative for peptides in general.