Kallikreins and Kinins

  • V. Eisen
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 87 / 1)


This article has two aims:
  1. 1.

    To describe briefly the general aspects of kinins and the factors concerned with the formation and removal of kinins, so as to enable the reader to evaluate the role kinins may play in healthy and diseased skin. Comprehensive accounts of older and recent work on the kinin system with extensive lists of references may be found in two volumes of this Handbook (ERDÖS 1970,1979 a) and in numerous monographs, reviews and proceedings of learned meetings (Frey et al. 1968; SCHACHTER 1969, 1980; ERDOS 1976; HABERLAND et al. 1973–1977; EISEN 1970, 1980; PISANO and AUSTEN 1976; HABERLAND 1978; FUJII et al. 1979; REGOLI and BARABE 1980; FRITZ et al. 1982,1983; GREENBAUM and MARGOLIUS 1986).

  2. 2.

    To discuss more fully the literature dealing specifically with kinins as factors in the physiology and pathology of the skin.



Plasma Kallikrein High Molecular Weight Kininogen Urticaria Pigmentosa Proteolytic Inhibitor Glandular Kallikrein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Barrett AJ, Starkey PM (1973) The interaction of α2-macroglobulin with proteinases. Biochem J 133:709–724PubMedGoogle Scholar
  2. Beck PW, Handwerker HO (1974) Bradykinin and serotonin effects on various types of cutaneous nerve fibres. Pflügers Arch 347:209–222CrossRefPubMedGoogle Scholar
  3. Black AK, Greaves MW, Hensby CN, Plummer NA (1976) A new method of obtaining human skin inflammatory exudate for pharmacological analysis. Br J Pharmacol 58:317Google Scholar
  4. Carter RD, Joyner WL, Renkin EM (1974) Effect of histamine and some other substances on molecular selectivity of the capillary wall to plasma proteins and dextran. Microvasc Res 7:31–48CrossRefPubMedGoogle Scholar
  5. Chahl LA, Iggo A (1977) The effects of bradykinin and prostaglandin E1 on rat cutaneous afferent nerve activity. Br J Pharmacol 59:343–347PubMedGoogle Scholar
  6. Chung DW, Fujikawa K, McMullen BA, Davie EW (1986) Human plasma kallikrein, a zymogen to a serine protease that contains four tandem repeats. Biochemistry 25:2410CrossRefPubMedGoogle Scholar
  7. Cochrane CG, Griffin J (1979) Molecular assembly in the contact phase of the Hageman factor system. Am J Med 67:657–664CrossRefPubMedGoogle Scholar
  8. Cochrane CG, Revak SD (1980) Dissemination of contact activation in plasma by plasma kallikrein. J Exp Med 152:608–619CrossRefPubMedGoogle Scholar
  9. Curd JG, Prograis LJ, Cochrane CG (1980) Detection of active kallikrein in induced blister fluids of hereditary angioedema patients. J Exp Med 152:742–747CrossRefPubMedGoogle Scholar
  10. DeLaus FW, Winkelmann RK (1968) Kinins in cold urticaria. Arch Dermatol 98:67–74CrossRefPubMedGoogle Scholar
  11. Dorer FE, Kahn JR, Lentz KE, Levine M, Skeggs LT (1974) Hydrolysis of bradykinin by angiotensin-converting enzyme. Circ Res 34:824–827PubMedGoogle Scholar
  12. Eisen V (1963) Observations on intrinsic kinin-forming factors in human plasma:the effect of acid, acetone, chloroform, heat and euglobulin separation on kinin formation. J Physiol 166:496–513PubMedGoogle Scholar
  13. Eisen V (1964) Effect of hexadimethrine bromide on plasma kinin formation, hydrolysis of p-tosyl-l-arginine methyl ester and fibrinolysis. Br J Pharmacol 22:87–103Google Scholar
  14. Eisen V (1970) Formation and function of kinins. In:Rotstein J (ed) The immunochemistry and biochemistry of connective tissue and its disease states. Rheumatology, vol 3. Karger, Basel, pp. 103–168Google Scholar
  15. Eisen V (1980) Kinins in physiology and pathology. Trends Pharmacol Sci 8:212–215Google Scholar
  16. Eisen V, Glanville KLA (1969) Separation of kinin-forming factors in human plasma. Br J Exp Pathol 50:427–437PubMedGoogle Scholar
  17. Erdös EG (ed) (1970) Bradykinin, kallidin and kallikrein. Handbook of experimental pharmacology, vol 25. Springer, Berlin Heidelberg New YorkGoogle Scholar
  18. Erdös EG (1976) The kinins:a status report. Biochem Pharmacol 25:1663–1669CrossRefGoogle Scholar
  19. Erdös EG (ed) (1979 a) Bradykinin, kallidin and kallikrein. Handbook of experimental pharmacology, vol 25, supplement. Springer, Berlin Heidelberg New YorkGoogle Scholar
  20. Erdös EG (1979 b) Inhibitors of kininases. Fed Proc 38:2774–2777Google Scholar
  21. Erdös EG, Johnson AR, Boyden NT (1978) Hydrolysis of enkephalin by cultured human endothelial cells and by purified peptidyl dipeptidase. Biochem Pharmacol 27:843–848CrossRefPubMedGoogle Scholar
  22. Feldberg W, Lewis GP (1964) The action of peptides on the adrenal medulla:release of adrenaline by bradykinin and angiotensin. J Physiol 171:98–108PubMedGoogle Scholar
  23. Ferreira SH (1972) Prostaglandins, aspirin-like drugs and analgesia. Nature New Biol 240:200–203CrossRefPubMedGoogle Scholar
  24. Ferreira SH (1980) Peripheral analgesia:mechanism of the analgesic action of aspirin-like drugs and opiate antagonists. Br J Clin Pharmacol 10:237–245Google Scholar
  25. Fox RH, Hilton SM (1958) Bradykinin formation in human skin as a factor in heat vasodilatation. J Physiol 142:219–232PubMedGoogle Scholar
  26. Frewin DB, McConnell DJ, Downey JA (1973) Is kininogenase necessary for human sweating? Lancet 11:744CrossRefGoogle Scholar
  27. Frey EK, Kraut H, Werle E (1968) Das Kallikrein-Kinin-System und seine Inhibitoren. Enke, StuttgartGoogle Scholar
  28. Fritz H, Fink E, Truscheit E (1979) Kallikrein inhibitors. Fed Proc 38:2753–2759PubMedGoogle Scholar
  29. Fritz H, Dietze G, Fiedler F, Haberland GL (eds) (1982) Recent progress on kinins. Agents and actions (open)Suppl(close), vol 9. Birkhäuser, Basel Boston StuttgartGoogle Scholar
  30. Fritz H, Back N, Dietze G, Haberland GL (eds) (1983) Kinins — III. Adv Exp Med Biol 156Google Scholar
  31. Fujii S, Moriya H, Suzuki T (eds) (1979) Kinins — II. Adv Exp Med Biol 120:parts A and B. Plenum, New YorkGoogle Scholar
  32. Gordon C, Schwarz V (1971) Cyclic AMP, bradykinin and sweat gland function. J Physiol 213:68–69Google Scholar
  33. Greaves MW, Shuster S (1967) Responses of skin blood vessels to bradykinin, histamine and 5-hydroxytryptamine. J Physiol 193:255–267PubMedGoogle Scholar
  34. Greaves MW, Søndergaard J (1970 a) Pharmacologic agents released in ultraviolet inflammation studied by continuous skin perfusion. J Invest Dermatol 54:365–367CrossRefGoogle Scholar
  35. Greaves MW, Søndergaard J (1970 b) Urticaria pigmentosa and factitious urticaria. Direct evidence for release of histamine and other smooth muscle-contracting agents in dermographic skin. Arch Dermatol 101:418–425CrossRefGoogle Scholar
  36. Greaves MW, Søndergaard J (1970 c) A new pharmacological finding in human allergic contact eczema. Arch Dermatol 101:659–661CrossRefGoogle Scholar
  37. Greaves MW, Birkett D, Johnson C (1970) Nevus anaemicus:a unique catecholamine-de-pendent nevus. Arch Dermatol 102:172–176CrossRefPubMedGoogle Scholar
  38. Greaves MW, Birkett D, Johnson C (1970) Nevus anaemicus: a unique catecholamine-dependent nevus. Arch Dermatol 102:172–176CrossRefPubMedGoogle Scholar
  39. Greaves MW, Søndergaard JS, Holt G, McDonald-Gibson W (1971 b) Recovery of prostaglandin-like fatty acids from human allergic contact eczema by the use of a skin perfusion method. J Pathol 103:8–9Google Scholar
  40. Greenbaum LM (1979) Kininogenases of blood cells (alternate kinin generating systems). In:Erdos EG (ed) Bradykinin, kallidin and kallikrein. Springer, Berlin Heidelberg New York, pp. 91–102 (Handbook of experimental pharmacology, vol 25, supplement)Google Scholar
  41. Greenbaum LM, Margolius HS (eds) (1986) Kinins — IV. Adv Exp Med Biol 198:parts A and BGoogle Scholar
  42. Griffin JH (1978) Role of surface in surface-dependent activation of Hageman factor (blood coagulation factor XII). Proc Natl Acad Sci USA 75:1998–2002CrossRefPubMedGoogle Scholar
  43. Haberland GL (1978) The role of kininogenases, kinin formation and kininogenase inhibition in post traumatic shock and related conditions. Klin Wochenschr 56:325–331CrossRefPubMedGoogle Scholar
  44. Haberland GL, McConn R (1979) A rationale for the therapeutic action of aprotinin. Fed Proc 38:2760–2767PubMedGoogle Scholar
  45. Haberland GL, Rohen JW, Suzuki T, Blumel G, Schirren C, Huber P (1973–1977) Kininogenases, vols 1–4. Schattauer, StuttgartGoogle Scholar
  46. Hilton SM (1970) The physiological role of glandular kallikreins. In:Erdös EG (ed) Bradykinin, kallidin and kallikrein. Springer, Berlin Heidelberg New York, pp. 389–399 (Handbook of experimental pharmacology, vol 25Google Scholar
  47. Iggo A (1976) Peripheral and spinal “pain” mechanisms and their modulation. In:Bonica JJ, Albe-Fessard D (eds) Advances in pain research and therapy, vol 1. Raven, New York, pp. 381–394Google Scholar
  48. Ikeda K, Tanaka K, Katori M (1975) Potentiation of bradykinin-induced vascular permeability increase by prostaglandin E2 and arachidonic acid in rabbit skin. Prostaglandins 10:747–758PubMedGoogle Scholar
  49. Innis RB, Manning DC, Stewart JM, Snyder SH (1981) [3H] Bradykinin receptor binding in mammalian tissue membranes. Proc Natl Acad Sci USA 78:2630–2634CrossRefPubMedGoogle Scholar
  50. Johnson AR (1979) Effects of kinins on organ systems. In:Erdös EG (ed) Bradykinin, kallidin and kallikrein. Springer, Berlin Heidelberg New York, pp. 357–399 (Handbook of experimental pharmacology, vol 25, supplement)Google Scholar
  51. Joyner WL, Carter RD, Raizes GS, Renkin EM (1974) Influence of histamine and some other substances on blood-lymph transport of plasma protein and dextran in the dog paw. Microvasc Res 7:19–30CrossRefPubMedGoogle Scholar
  52. Junnila SK, Jansen CT, Hopsu-Havu VK (1971) Elastase and trypsin inhibitors of human skin and serum. Partial purification and characterization. Acta Derm Venereol (Stockh) 51:251–256Google Scholar
  53. Keele CA, Armstrong D (1964) Substances producing pain and itch. Arnold, LondonGoogle Scholar
  54. Kunitz M, Northrop JH (1936) Isolation from beef pancreas of crystalline trypsinogen, trypsin, trypsin inhibitor and an inhibitor-trypsin compound. J Gen Physiol 19:991–1007CrossRefPubMedGoogle Scholar
  55. Landerman NS, Webster ME, Becker EL, Ratcliffe HE (1962) Hereditary angioneurotic edema. Deficiency of inhibitor for serum-globulin-permeability factor and/or plasma kallikrein. J Allergy 3:330–341CrossRefGoogle Scholar
  56. Leckie BJ (1981) Inactive renin:an attempt at a perspective. Clin Sci 60:119–130PubMedGoogle Scholar
  57. Lewis GP, Reit E (1965) The action of angiotensin and bradykinin on the superior cervical ganglion of the cat. J Physiol 179:538–553PubMedGoogle Scholar
  58. Majno E, Shea SM, Leventhal M (1969) Endothelial contraction induced by histamine type mediators:an electron microscopic study. J Cell Biol 42:647–672CrossRefPubMedGoogle Scholar
  59. McGiff JC (1980) Interactions of prostaglandins with the kallikrein-kinin and renin-angiotensin systems. Clin Sci 59:105–116Google Scholar
  60. Michaelsson G (1970 a) Effects of antihistamines, acetylsalicylic acid and prednisone on cutaneous reactions to kallikrein and prostaglandin Ex. Acta Derm Venereol (Stockh) 50:31–36Google Scholar
  61. Michaelsson G (1970 b) Decreased cutaneous reactions to kallikrein in patients with atopic dermatitis and psoriasis. Acta Derm Venereol (Stockh) 50:37–41Google Scholar
  62. Moncada S, Ferreira SH, Vane JR (1973) Prostaglandins, aspirin-like drugs and the oedema of inflammation. Nature 246:217–219CrossRefPubMedGoogle Scholar
  63. Movat HZ (1979) The plasma kallikrein-kinin system and its interrelationship with other components of blood. In:Erdos EG (ed) Bradykinin, kallidin and kallikrein. Springer, Berlin Heidelberg New York, pp. 1–89 (Handbook of experimental pharmacology, vol 25, supplement)Google Scholar
  64. Newball HH, Berninger RW, Talamo RC, Lichtenstein M (1979) Anaphylactic release of a basophil kallikrein-like activity. I and II. J Clin Invest 64:457–465, 466–475CrossRefPubMedGoogle Scholar
  65. Nossel HL (1966) Activation of factors XII (Hageman) and XI (PTA) by skin contact. Proc Soc Exp Biol Med 122:16–17PubMedGoogle Scholar
  66. Ogston D, Ogston CM, Ratnoff OD (1969) Studies on the clot-promoting effect of skin. J Lab Clin Med 73:70–77PubMedGoogle Scholar
  67. Pisano JJ (1979) Kinins in nature. In:Erdos EG (ed) Bradykinin, kallidin and kallikrein. Springer, Berlin Heidelberg New York, pp. 273–285 (Handbook of experimental pharmacology, vol 25, supplement)Google Scholar
  68. Pisano JJ, Austen KF (eds) (1976) Chemistry and biology of the kallikreinkinin system in health and disease. Fogarty Intern Center Proc, vol 27. US Government Printing Office, Washington DCGoogle Scholar
  69. Plummer NA, Hensby CN, Black AK, Greaves MW (1977) Prostaglandin activity in sustained inflammation of human skin before and after aspirin. Clin Sci Mol Med 52:615–620PubMedGoogle Scholar
  70. Regoli D, Barabe J (1980) Pharmacology of bradykinin and related kinins. Pharmacol Rev 32:1–46PubMedGoogle Scholar
  71. Regoli D, Barabe J, Park WK (1977) Receptors for bradykinin in rabbit aortae. Can J Physiol Pharmacol 55:855–867CrossRefPubMedGoogle Scholar
  72. Rocha e Silva M, Beraldo WT, Rosenfeld G (1949) Bradykinin, a hypotensive and smooth muscle stimulating factor released from plasma globulin by snake venoms and by trypsin. Am J Physiol 156:261–273PubMedGoogle Scholar
  73. Ryan JW, Ryan US (1976) Biochemical and morphological aspects of the actions and metabolism of kinins. In:Pisano JJ, Austen KF (eds) Chemistry and biology of the kallikrein-kinin system in health and disease. Fogarty Intern Center Proc 27:315–333, US Government Printing Office, Washington DCGoogle Scholar
  74. Saameli K, Eskes TKAB (1962) Bradykinin and cardiovascular system:estimation of half-life. Am J Physiol 203:261–265PubMedGoogle Scholar
  75. Schachter M (1969) Kallikreins and kinins. Physiol Rev 49:510–547Google Scholar
  76. Schachter M (1980) Kallikreins (kininogenases) — a group of serine proteases with bioregulatory actions. Pharmacol Rev 31:1–17Google Scholar
  77. Schwartz LB, Maier M, Spragg J (1986) Interaction of human LMWK with human mast cell tryptase. In: Greenbaum LM, Margolius HS (eds) Kinins — IV. Adv Exp Med Biol 198A:105–111Google Scholar
  78. Shayman JA, Morrison AR (1985) Bradykinin-induced changes in phosphatidyl inositol turnover in cultured rabbit papillary collecting tubule cells. J Clin Invest 76:978CrossRefPubMedGoogle Scholar
  79. Søndergaard J, Greaves MW (1970a) Pharmacological studies in inflammation due to exposure to ultraviolet radiation. J Pathol 101:93–97CrossRefPubMedGoogle Scholar
  80. Søndergaard J, Greaves MW (1970b) The responses of the skin to tetrahydrofurfuryl nicotinate (Trafuril) studied by continuous skin perfusion. Br J Dermatol 82:14–18CrossRefPubMedGoogle Scholar
  81. Søndergaard J, Greaves MW (1971) Direct recovery of histamine from cutaneous anaphylaxis in man. Acta Derm Venereol (Stockh) 51:98–100Google Scholar
  82. Stewart JM (1979) Chemistry and biologic activity of peptides related to bradykinin. In:Erdos EG (ed) Bradykinin, kallidin and kallikrein. Springer, Berlin Heidelberg New York, pp.227–272 (Handbook of experimental pharmacology, vol 25, supplement)Google Scholar
  83. Toki N, Yamura T (1978) Plasma-kinin-forming enzyme in human skin:extraction and column, chromatographic separation of plasma-kinin-forming enzyme and its inhibitor. Acta Derm Venereol (Stockh) 58:395–399Google Scholar
  84. Toki N, Yamura T (1979) Kinin-forming enzyme in human skin:the purification and characterization of a kinin-forming enzyme. J Invest Dermatol 73:297–302CrossRefPubMedGoogle Scholar
  85. Toki N, Yamura T (1980) Further studies on a new kallikrein inhibitor in human skin -its purification and characterization. Arch Dermatol Res 267:301–311CrossRefPubMedGoogle Scholar
  86. Vane JR (1969) The release and fate of vasoactive hormones in the circulation. Br J Pharmacol 35:209–242PubMedGoogle Scholar
  87. Vogt W, Dugal B (1976) Generation of an esterolytic and kinin-forming kallikrein-α2-macroglobulm complex in human serum treated with acetone. Naunyn Schmiedebergs Arch Pharmacol 294:75–82CrossRefPubMedGoogle Scholar
  88. Wendt P, Bliimel G (1979) Neutral proteases from granulocytes and their inhibitors. In:Haberland GL, Hamberg U (eds) Current concepts in kinin research. Pergamon Press, Oxford and New York, pp. 73–81Google Scholar
  89. Wiggins RC, Cochrane CG (1979) The autoactivation of rabbit Hageman factor. J Exp Med 150:1122–1133CrossRefPubMedGoogle Scholar
  90. Wiggins RC, Giclas PC, Henson PM (1981) Chemotactic activity generated from the fifth component of complement by plasma kallikrein of the rabbit. J Exp Med 153:1391–1404CrossRefPubMedGoogle Scholar
  91. Williams TJ, Morley J (1973) Prostaglandins as potentiators of increased vascular permeability in inflammation. Nature 246:215–217CrossRefPubMedGoogle Scholar
  92. Williams TJ, Peck MJ (1977) Role of prostaglandin-mediated vasodilatation in inflammation. Nature 270:530–532CrossRefPubMedGoogle Scholar
  93. Williams K, Rosen FS, Donaldson VH (1975) Observations on the ultrastructure of lesions induced in human and guinea pig skin by CI esterase and polypeptide from hereditary angioneurotic edema (HANE) plasma. Clin Immunol Immunopathol 4:174–188CrossRefGoogle Scholar
  94. Wilner GD, Nossel HL, LeRoy EC (1968) Activation of Hageman factor by collagen. J Clin Invest 47:2608–2615CrossRefPubMedGoogle Scholar
  95. Winkelmann RK, Wilhelm CM, Horner FA (1965) Experimental studies on dermographism. Arch Dermatol 92:436–442CrossRefPubMedGoogle Scholar
  96. Winkelmann RK, Vesper LJ, Horner FA (1966) Histamine release from the skin of patients with cutaneous mast cell disease (urticaria pigmentosa). Acta Derm Venereol (Stockh) 46:279–284Google Scholar
  97. Zacest R, Oparil S, Talamo RC (1974) Studies of plasma bradykininases using radiolabeled substrates. Aust J Exp Biol Med Sci 52:601–606CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • V. Eisen

There are no affiliations available

Personalised recommendations