Distribution and metabolism of secretin and aprotinin in isolated perfused rat pancreas.

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Abstract
The distribution and metabolism of secretin and aprotinin were studied in isolated perfused rat pancreas, which were kept under physiological conditions. At 125I-[Tyr1]secretin perfusion study the radioactivity appeared in the effluent, rapidly attaining an equilibrium with the perfusate. While the intact secretin concentration decreased to 55% of the perfusate, the distribution space of secretin was estimated to be .apprx. 0.11 ml/g pancreas. The ratio of intact secretin to degraded products in the pancreas increased concomitantly with the perfusion of 82 nM secretin. When unlabeled secretin was perfused, immunoreactive secretin concentration in the portal effluent also reached a rapid equilibrium to .apprx. 60% of the perfusate. Pancreas might clear .apprx. 40% of the entering secretin. In the case of 125I-aprotinin perfusion, intact aprotinin fraction was predominant both in the effluent and in the pancreas. The apparent distribution space was .apprx. 40% of the volume of pancreas. When 125I-reduced aprotinin or 125I-[S-carboxamidomethyl]aprotinin was perfused, the decomposed products were significantly increased. Evidently, the disulfide bonds in aprotinin molecule play an important role for its stability as well as its antiproteolytic activity.