Bradykinin is frequently referred to as an elusive substance; the editor of a comprehensive volume dealing with kinins thus has a difficult task. The com­ plexity of the issues calls for a large number of contributors who approach the topics from the various angles that are dictated by the sometimes divergent views of the individuals. The editor saw no reason to prescribe the mode of presentation, which was left to the authors and accounts for the variety of approaches. Contributors from nine countries were asked to participate in the volume. The chapters were organized to present, first, the history of the discoveries and methods of approach to kinin research. Then follows a discussion of the enzymes that release kinins, their substrates, and other enzymes that inactivate the peptides. If the release of kinin is important, then the inhibition of the releasing enzymes is of obvious interest and is described. Since the measurement of kinin­ ogen levels in blood has been frequently used as an indicator of kinin liberation, in addition to a separate chapter, kininogens are also mentioned where the functions of kinins are discussed. The conclusions drawn from establishing structure-action relationships for many analogs and the actions of kinins are indicated and summarized.

Inhalt

1: Introduction.- Discovery of the Most Important Kallikreins and Kallikrein Inhibitors.- A. Discovery of Kallikrein from Urine.- B. Discovery of the Kallikrein Inhibitor of Blood Serum.- C. Discovery of F-Substance in Pancreas.- D. Discovery of Kallikrein in Salivary Glands and Saliva.- E. Discovery of Kallikreinogen in Pancreas and Pancreas Secretion and in Other Organs.- F. Discovery of Plasma Kallikrein.- G. Discovery of the Kallikrein Inhibitor of Bovine Organs (Trasylol).- H. Discovery of Kallidin and the Enzymatic Nature of Kallikrein.- J. Detection of Kallidin-Inactivating Enzymes.- References.- The Discovery and Characterization of Bradykinin.- References.- 2: Methods Used in Kinin Research.- The Kinins: Methods of Chemical Synthesis.- A. Methods of Peptide Synthesis.- B. Synthesis of Bradykinin.- C. Synthesis of Kallidin.- D. Synthesis of Methionyl-Lysyl-Bradykinin.- E. Synthesis of Nonmammalian Kinins.- References.- Purification of Mammalian Kallikreins, Kininogens, and Kinins.- A. Introduction.- I. Methodological Considerations.- II. Reporting Purification Results.- III. Possibility of a Unified Approach to the Purification of Kallikrein and Kininogen Homologs and Kinins.- B. Plasma Kallikreins.- I. Hog Serum Kallikrein (Habermann and Klett, 1966).- II. Human Plasma Kallikrein (Webster and Pierce, 1963).- III. Bovine Plasma Prekallikrein (Nagasawa et al., 1968).- C. Pancreatic Kallikreins.- I. Hog Pancreatic Kallikrein (Method 1, Moriya et al., 1965b, 1969).- II. Hog Pancreatic Kallikrein (Method 2, Habermann, 1962).- D. Urinary Kallikreins.- I. Horse Urinary Kallikrein (Prano et al., 1962, 1963).- II. Human Urinary Kallikrein (Moriya et al., 1963).- E. Salivary Kallikreins.- I. Hog Submaxillary Kallikrein (Trautschold, 1965; Roder, 1967).- II. Human Salivary Kallikrein (Moriya et al., 1965a, 1966).- F. Low Molecular Weight Kininogens.- I. Bovine LMW Kininogen (Suzuki et al.).- II. Rabbit LMW Kininogen (Egorova and Paskhina, 1967; Egorova et al., 1969).- III. Human LMW Kininogens I and II (Pierce and Webster, 1966).- G. High Molecular Weight Kininogens.- I. Human HMW Kininogen (Jacobsen and Kriz, 1967).- II. Bovine UMW Kininogen (Yano et al., 1967b).- H. Kinins.- Procedure.- I. Preparation of the Extract.- II. IRC-50 Adsorption.- III. IRC-50 Elution.- IV. Gel Filtration.- V. CM-Cellulose and CM-Sephadex C-25 Chromatography.- VI. P-Cellulose Chromatography.- References.- Assay Methods in the Kinin System.- Kinins.- A. Isolated Smooth Muscle Preparations Used in the Bioassay of Kinins.- I. Guinea Pig Ileum.- II. Rat Uterus.- III. Miscellaneous Preparations.- IV. Superfusion Technique by Vane (1964) and Ferreira and Vane (1967).- B. Vascular Effect of the Kinins and Bioassay.- I. Blood Pressure Recorded from the Carotid Artery.- II. Blood Flow Bioassay Techniques for Vasoactive Substances.- C. Increase of the Capillary Permeability as Bioassay.- D. Radioimmunoassay of Kinins.- E. Assay of Free Kinins in the Blood and Urine.- I. Determination in Blood.- II. Determination in Urine.- Kininogen.- I. Pretreatment of the Plasma Kininogen.- II Kinin Release with Trypsin.- III. Kinin Release with Kallikrein and by Glass Activation.- Kininases.- I. Determination of the Kininase Activity with Kinins as Substrate.- II. Determination of the Kininase Activity with Synthetic Substrates.- III Kininase Units.- Kininogenases.- I. Estimation of Kininogenases by Bioassay.- II. Estimation of the Kininogenases with Synthetic Substrates.- Kininogenase Inhibitors.- References.- 3: Kininogenases.- Plasma Kininogenases and Their Activators.- A. Introduction.- B. Postulated Mechanisms of Intrinsic Plasma Kinin Formation.- I. Early Views on the Origin and Activation of Serum Prekallikrein.- II. The Fibrinolytic System.- III. The Contact System.- IV. The System of Globulin Permeability Factors.- V. The Kininogenase I and Kininogenase II System.- C. Activators.- I. Hageman Factor.- II. Permeability Factor (PF).- III. Plasmin (EC 3.4.4.14).- D. Kininogenases.- I. Plasma Kallikrein (EC 3.4.4.21).- II. Plasmin.- III. Kininogenase II.- IV Kinin-Forming Substance.- E. Differentiation of Kinin-Forming Enzymes and Activators of Plasma.- References.- Kallikreins in Glandular Tissues.- A. Introduction and History.- B. Subcellular Location and Activation of the Glandular Kallikreins.- C. Tissue Concentrations of the Glandular Kallikreins.- D. Purification and Some Properties of the Glandular Kallikreins.- E. The Active Center of the Kallikreins.- F. Species Differences Among the Glandular Kallikreins.- G. Detection and Identification of a Glandular Kallikrein.- References.- Proteolytie Enzymes as Kininogenases.- A. Introduction.- I. Terminology.- II. Kininogenases other than Kallikreins and Snake Venom Enzymes.- B. Chemistry.- I. Trypsin.- II. Pepsin.- III. Clostripain.- IV. Subtilisin BPN' (Nagarse).- V. Ficin.- VI. Papain.- VII. Streptomyces griseus Protease (Pronase).- VIII. Carboxypeptidase A.- IX. Chymotrypsin.- C Kinin Formation.- I. Demonstration of Kinin-Forming Activity.- II. Nature of Kinin Liberated.- III. Action on the Substrate.- IV. Relative Kinin-Forming Activity.- V. Specificity.- D Kininase Activity.- E. Other Pharmacological Effects.- I. Stimulating Effect on Smooth Muscles.- II. Shock.- III. Pruritus.- References.- Snake Venoms.- A. Bradykinin-Releasing Enzyme in Snake Venom.- B. Purification of Bradykinin-Releasing Enzyme (Kininogenase) from Snake Venom.- C. Dependency of the Kininogenase on the Arginine Esterase in the Venom.- D. The Kinin Liberated by Venom Enzymes and the Properties of Kininogenase in Venoms.- E. Kininases and Bradykinin Potentiators in Snake Venoms.- References.- Kallikrein Inhibitors.- A. Introduction.- B. Kallikrein Blocking Agents.- C Immune Bodies Against Kallikreins.- D. Natural Kallikrein Inhibitors.- I. Units.- II. Methods of Determination.- III. Plant Inhibitors.- IV Inhibitors of Animal and Human Origin.- E. Kallikrein-Destroying Enzymes.- References.- 4: Kininogens.- Kininogens.- A. History and Definition.- B. Estimation.- I. Important Factors.- II. Typical Procedures for Kinin Release.- C. Isolation and Biochemical Properties.- I. Bovine Kininogens.- II. LMW Human Kininogens.- III. Horse Kininogens.- IV. LMW Rabbit Kininogen.- D Kinin Release and Its Relationship to the Structure of Kininogens.- I. Bovine LMW Kininogen.- II. Human Kininogens.- E. Kininogen Level in vivo.- I. General Considerations.- II. Normal Kininogen Values.- III. Variations of Kininogen Level.- References.- 5: Kininases.- Kininases.- A. Blood.- I. Carboxypeptidase N.- II Kininase II.- III. Blood Cells.- B. Other Biological Fluids.- C. Tissues.- D. Purified Proteolytic…