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It is generally assumed that the pharmacological action of a biologically active substance, which is synthesized by the body, is, in some way, paralleled by its physiological function. Provided that selective inhibition of distinct proteolyticesterolytic enzymes is the sole function of naturally occurring proteinase-inhibitors and that synthesis of these inhibitors is not merely a rudimental and now meaningless genetic cell-function, the physiological function of these inhibitors is selective inhibition of enzymatic-proteolytic processes. They probably also protect tissues against undue activation of proteolytic enzymes.Inhibitors, which only occur in certain species and, even in these, only in certain organs, and which do not occur in interstitial and other body fluids (TABLE l ) , probably inhibit and regulate enzymatic reactions at an intracellular level. This applies to the polyvalent trypsin-kallikrein-inhibitor from bovine organs, which occurs also in secretory organs like salivary glands and pancreas, but is not found in secretions of these organs nor in other body fluids (Frey et al., 1950). Stimulation-e.g., by pilocarpin-which usually results in an unphysiological high secretion rate, does not bring about any secretion of inhibitor. Following i.v. injection of pure preparations of trypsin-kallikrein-inhibitor from bovine organs up to 10,000 KIU/kg in cattle, dogs, and hogs, we could not demonstrate the inhibitor in saliva nor in pancreatic juice. Furthermore, the inhibitor reaching salivary glands and pancreas via the bloodstream did not accumulate in these organs. On isolated perfusion of dog pancreas, addition of Trasylol@ to the perfusion fluid does not. impair secretion of zymogens or insulin.From our former experiments, we know that intravenous Trasylol is distributed to the various organs according to their blood supply (FIGURE 1 ) . Following injection of 12,000 KIU/kg in rats and 3500 KIU/kg in dogs, inhibitor concentration in the liver attains a temporary maximum after 30 min. After a latent interval of about 10 min, inhibitor concentrations begins to increase in the kidneys. One hour after injection, the inhibitor content in renal tissue is higher than in the liver (50% and 36% respectively of the total amount). The blood still contains less than 10% of the injected inhibitor amount. About five hours after injection, almost the entire amount of inhibitor administered is to be found in an active form in the kidneys. The results suggest that the inhibitor undergoes structural change in the liver which condition it for fixation in the kidney. Using tritiumlabeled Trasylol, we could show that, before excretion, the bulk of inhibitor is degraded and is demonstrable in urine as tritium activity only (FIGURE 2) (Traut- schold et ul., 1964).As the trypsin-kallikrein-inhibitor occurs selectively in cattle and perhaps more generally in ruminants, a physiological function can be discussed for this species only. From the information available to us, we believe this inhibitor is identical with the inhibito...

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Zusammenfassung: Menschliches Nasensekret hemmt proteolytische Enzyme wie Trypsin, Chymotrypsin und Pronase. Plasmin, Kallikrein, Subtilopeptidase A und Pankreatopeptidase E werden nicht gehemmt. Die gesamte hemmende Aktivität des Sekrets tritt bei Gelfiltration in einem symmetrischen Gipfel aus der Trennsäule aus. Es kann angenommen werden, daß die Hemmung der Enzyme durch einen polyvalenten Inhibitor bewirkt wird. Der Inhibitor gehört zur Klasse der sog. Lysin-* Die Arbeit wurde mit Mitteln des SFB 51 der DEUTSCHEN FORSCHUNGSGEMEINSCHAFT gefördert.