Frey - Werle - Foundation

The surgeon Emil-Karl Frey, a scholar of the famous ‘Geheimrat’ Ferdinand Sauerbruch, observed in 1925 a considerable reduction in arterial blood pressure when he injected human urine into dogs. Unlike many other contemporary scientists he did not attribute this effect to a toxic action of urine, but rather as the specific activity of an unknown substance with potential biological functions (Frey, 1926; Frey and Kraut, 1926): “It is a substance that probably originates from several organs, is eliminated by the kindneys and has a pronounced cardioactive and vasoactive effect: a substance that is assigned the role of a hormone in the organism”. This F-substance was then called kallikrein, since it was considered to have originated in the pancreas (Greek synonym: kallikreas) (Kraut et al, 1930).

Ten years later, Eugen Werle (Werle et al., 1937) identified kallikrein as a proteolytic enzyme (‘ferment’) that liberates the biologically highly active, basic polypeptide ‘DK’ or kallidin (i.e lys-bradykinin) from a blood plasma protein called kallidinogen or kininogen (H- and L-kininogen). Hence, kallidin was the first of the basic peptides formed by proteolysis to be identified as a hormone, and later became known as lys-bradykinin, a member of the family of biologically active kinin peptides. Kallidin was first characterized in great detail, especially withregard to its manifold pharmacological effects (Frey et al., 1950). Werle also observed for the first time irreversible ‘fermental degradation’ of kallidin by ‘kininases’ and identified them as peptidases (Werle and Grunz, 1939). Therefore, the fundamental knowledge of the system that we refer to today as the kallikrein-kinin system (cascade) was provided by Frey, Kraut and Werle.

The vital importance of the kallikrein-kinin system for basic mechanisms in biochemistry, patho/physiology, pharmacology and more recently, molecular biology and cell biology, and the great interest and practical benefit of the system to clinical medicine, has stimulated scientists from various disciplines worldwide to become involved in kallikrein-kinin research. Among them are scientists working also on various regulatory or mediator systems that interact with the kallikrein-kinin cascade. A drug based on the seminal research designated as angiotensin I converting enzyme (ACE)inhibitor has been shown to be of immense value in the treatment of coronary heart disease. This drug simultaneously blocks the ACE-catalyzed degradation of kinins and the generation of angiotensin II, two tissue hormones that exhibit opposite biological or pharmacological effects.