Skip to main content
SpringerLink
Log in

On the endogenous mechanism of kinin release

I. Attempts at discriminating kallikreins

  • Published:
Naunyn-Schmiedebergs Archiv für Pharmakologie Aims and scope Submit manuscript

Summary

  1. 1.

    Prekallikrein, prepared according to Nagasawaet al., has been purified further by agarose gel electrophoresis. It can be activated directly by Hageman factor and by solid phase trypsin. Its specific activity (benzoyl arginine ethyl ester as substrate) was 13.2 μM min−1 mg−1. Gel filtration on a calibrated column of sephadex G 200 revealed a molecular weight of 101,000, which is close to the value reported for casein-activated kallikrein.

  2. 2.

    The contact-activated bovine enzyme was very similar to casein-activated porcine kallikrein. Both enzymes hydrolyzed benzoyl arginine ethyl ester and tosylarginine methyl ester with about the same speed. The sensitivity of the two preparations against trasylol®, soy bean inhibitor, and serum inhibitor was also not different.

  3. 3.

    In contrast to previous assumptions, purified bovine LMW kininogen (MW 50,000) proved to be substrate for contact-activated kallikrein. As with the caseinactivated enzyme, the total bradykinin content of the kininogen could be released.

  4. 4.

    Serum, even when heated previously to 61°C, contains inhibitors against kallikreins activated by contact or casein, as well as against trypsin. Whereas pretreatment according to Diniz and Carvalho (pH about 2; 98°C) renders the serum more susceptible to trypsin, such denaturated substrate is less accessible for both kallikreins. Serum or plasma pretreated according to Horton (pH2; 37°C), yield at least 50% of the kinin activity obtained with trypsin, irrespective of the kallikreins used.

  5. 5.

    When acid-treated (according to Horton) 61°-serum has been incubated first with casein-activated kallikrein, contact-activated enzyme does not release additional kinin activity and vice versa.

  6. 6.

    Plasma which has been rotated exhaustively with glass, nevertheless contains substrate for contact-activated kallikrein.

  7. 7.

    Addition of Hageman factor to Horton's substrate does not increase the kinin yield above that obtained by glass-contact of normal plasma. Addition of prekallikrein, however, increases the kinin yield about threefold. Therefore, neither Hageman factor nor substrate, but the actual amount of active kallikrein limits the kinin yield upon glass activation.

  8. 8.

    Our experiments with serum kallikreins and their substrates can be interpreted without assuming a distinct, contact activated kinin system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aarsen, P. N.: Sensitization of guinea-pig ileum to the action of bradykinin by trypsin hydrolysate of ox and rabbit plasma. Brit. J. Pharmacol.32, 453–465 (1968).

    Google Scholar 

  • Andrews, P.: The gel-filtration behaviour of proteins related to their molecular weights over a wide range. Biochem. J.96, 595–606 (1965).

    Google Scholar 

  • Arndts, D.: Radioimmunologische Ultramikrobestimmungen von Proteinen und Polypeptiden: Entwicklung, Vergleich und Anwendungsmöglichkeiten. Inaug.- Diss., Gießen 1968.

  • Colman, R., Mattler, M., Sherry, S.: Studies on prekallikrein (kallikreinogen)-kallikrein enzyme system of human plasma. I. Isolation and purification of plasma kallikreins. II. Evidence relating the koalin-activated arginine esterase to plasma kallikrein. J. clin. Invest.48, 11–32 (1969).

    Google Scholar 

  • Diniz, C. R., Carvalho, J. E.: A micro method for determination of bradykininogen under several conditions. Ann. N. Y. Acad. Sci.104, 77–89 (1963).

    Google Scholar 

  • Eisen, V.: Observations on intrinsic kinin-forming factors in human plasma: the effect of acid, acetone, chloroform, heat and euglobulin separation on kinin formation. J. Physiol. (Lond.)166, 496–513 (1963).

    Google Scholar 

  • —: Enzymic aspects of plasma kinin formation. Proc. roy. Soc. B173, 351–359 (1969).

    Google Scholar 

  • —, Glanville, K. L. A.: Separation of kinin-forming factors in human plasma. Brit. J. exp. Path.50, 427–437 (1969).

    Google Scholar 

  • —, Keele, C. A.: Intrinsic plasma kinin forming factors in human plasma. J. Physiol. (Lond.)154, 20P-22P (1960).

    Google Scholar 

  • —, Vogt, W.: Plasma kininogenases and their activators. In: Handbook of Experimental Pharmacology, vol 25, pp. 82–130. Berlin-Heidelberg-New York: Springer 1970.

    Google Scholar 

  • Habermann, E.: Trennung und Reinigung von Pankreaskallikreinen, Hoppe Seylers Z. physiol. Chem.328, 15–23 (1962).

    Google Scholar 

  • —: Über pH-bedingte Modifikationen des kininliefernden α-Globulins (Kininogen) aus Rinderserum und das Molekulargewicht von Kininogen I. Biochem. Z.337, 440–448 (1963).

    Google Scholar 

  • —: Inhibitors of kallikrein and other proteinases from animal blood. Ann. N. Y. Acad. Sci.146, 479–490 (1968).

    Google Scholar 

  • —: Kininogens. In: Handbook of Experimental Pharmacology, vol. 25, pp. 250 to 288. Berlin-Heidelberg-New York: Springer 1970.

    Google Scholar 

  • —, Blennemann, G.: Über Substrate und Reaktionsprodukte der kininbildenden Enzyme Trypsin, Serum- und Pankreaskallikrein sowie von Crotalusgift. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.249, 357–373 (1964).

    Google Scholar 

  • —, Jahrreiss, R.: On the endogenous mechanism of kinin release. II. Attempts at discriminating kininogens. Naunyn-Schmiedebergs Arch. Pharmak.269, 101 to 111 (1971).

    Google Scholar 

  • —, Klett, W.: Reinigung und einige Eigenschaften eines Kallikreins aus Schweineserum. Biochem. Z.346, 133–158 (1966).

    Google Scholar 

  • Habermann, E., Klett, W., Rosenbusch, G.: Partielle Reinigung und einige Eigenschaften eines Kininogens aus Rinderblut. Hoppe Seylers Z. physiol.Chem.332, 121–142 (1963).

    Google Scholar 

  • Hamberg, U., Elg, P., Stelwagen, P.: Tryptic and plasmic peptide fragments increasing the effect of bradykinin on isolated smooth muscle. Scand. J. clin. Lab. Invest. (Suppl.)24, 21–50 (1969).

    Google Scholar 

  • Henriques, O. B., Stolpnik, V., Kusnetsova, V., Astrakan, M.: Glass-activated plasma kallikrein. Biochem. Pharmacol.19, 2915–2921 (1970).

    Google Scholar 

  • Horton, E. W.: The assay of kallikrein in urine. J. Physiol. (Lond.)142, 36P (1958).

    Google Scholar 

  • Jacobsen, S., Kriz, M.: Some data on two purified kininogens from human plasma. Brit. J. Pharmacol.29, 25–36 (1967).

    Google Scholar 

  • Jahrreiss, R., Habermann, E.: Isolierung und Struktur peptischer kininliefernder Peptide aus Rinderserum. Naunyn-Schmiedebergs Arch. Pharmak.264, 172 to 186 (1969).

    Google Scholar 

  • — —: In vitro investigations on some components of the kinin system (kininogen, serum kallikrein, Hageman factor) and their interaction. In F. Sicuteri (Ed): Bradykinin and related kinins: Cardiovascular, biochemical, and neural actions. New York-London: Plenum Press 1970.

    Google Scholar 

  • Kagen, L. J.: Some biochemical and biophysical properties of the human permeability globulins. Brit. J. exp. Path.45, 604 (1964).

    Google Scholar 

  • Kellermeyer, W. F., Kellermeyer, R. W.: Hageman factor activation and kinin formation in human plasma induced by cellulose-sulfate solutions. Proc. Soc. exp. Biol. (N. Y.)130, 1310–1314 (1969).

    Google Scholar 

  • Laufer, A. L., Gulikova, O. M., Paskhina, T. S.: Two kinin-producing enzymes from the blood plasma of man. Biokhimiya34, 3–12 (1969).

    Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the folin reagent. J. biol. Chem.193, 265–275 (1951).

    Google Scholar 

  • Margolis, J.: Activation of plasma by contact with glass: evidence for a common reaction which releases plasma kinin and initiates coagulation. J. Physiol. (Lond.)144, 1–22 (1958).

    Google Scholar 

  • —: Activation of Hageman factor by saturated fatty acids. Aust. J. exp. Biol.40, 505–514 (1962).

    Google Scholar 

  • —: Interrelationship of coagulation of plasma and release of peptides. Ann. N. Y. Acad. Sci.104, 133–145 (1963).

    Google Scholar 

  • —, Bishop, E. A.: Studies on plasma kinins. I. The composition of kininogen complex. Aust. J. exp. Biol.41, 293–306 (1963).

    Google Scholar 

  • Movat, H. Z., DiLorenzo, N. L., Treloar, M. P.: Activation of the plasma kinin system by antigen-antibody aggregates. II. Isolation of permeability-enhancing and kinin-releasing fractions from activated guinea pig serum. Lab. Invest.19, 201–210 (1968).

    Google Scholar 

  • - Poon, M.-Ch., Takeuchi, Y.: The kinin-system of human plasma. I. Isolation of a low molecular weight activator of prekallikrein. (In press.)

  • Nagasawa, S., Takahashi, H., Koida, M., Suzuki, T., Schoenmakers, J. G. G.: Partial purification of bovine plasma kallikreinogen, its activation by the Hageman factor. Biochem. biophys. Res. Commun.32, 644–649 (1968).

    Google Scholar 

  • Ratnoff, O. D.: Activation of Hageman factor by L-Homocystine. Science162, 1007–1009 (1968).

    Google Scholar 

  • —, Crum, J. D.: Activation of Hageman factor by solutions of ellagic acid. J. Lab. clin. Med.63, 359–377 (1964).

    Google Scholar 

  • Roberts, P. S.: Measurement of the rate of plasmin action on synthetic substrates. J. biol. Chem.232, 285–291 (1958).

    Google Scholar 

  • Schoenmakers, J. G. G., Matze, R., Haanen, C., Zilliken, F.: Hageman factor, a novel sialoglycoprotein with esterase activity. Biochim. biophys. Acta (Amst.)101, 166–176 (1963).

    Google Scholar 

  • Schwert, G. W., Takenaka, Y.: A spectrophotometric determination of trypsin and chymotrypsin. Biochim. biophys. Acta (Amst.)16, 570–575 (1955).

    Google Scholar 

  • Seidel, G., Vogt, W.: Kininogenspezifität von acetonaktiviertem menschlichem Plasmakallikrein. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path.262, 135–138 (1969).

    Google Scholar 

  • Suzuki, T., Iwanaga, S., Nagasawa, S., Sato, T.: Purification and properties of bradykininogen and of the bradykinin-releasing and destroying enzymes in snake venom. In: E. G. Erdös, N. Back, and F. Sicuteri: Hypotensive peptides pp. 149–160. Berlin-Heidelberg-New York: Springer 1966.

    Google Scholar 

  • Temme, H., Jahrreiss, R., Habermann, E., Zilliken, F.: Aktivierung von Gerinnungs- und Kininsystem durch eine Plasmaesterase (Hageman-Faktor). Reinigung und Wirkungsbedingungen. Hoppe Seylers Z. physiol. Chem.350, 519–521 (1969).

    Google Scholar 

  • Vogt, W., Garbe, G., Schmidt, G.: Untersuchungen zur Existenz zweier verschiedener kininbildender Systeme in menschlichem Plasma. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path.256, 127–138 (1967).

    Google Scholar 

  • —, Wawretschek, W.: Weitere Untersuchungen zur Existenz zweier kininbildender Systeme in menschlichem Plasma. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path.260, 223–230 (1968).

    Google Scholar 

  • Webster, M. E.: Human plasma kallikrein, its activation and pathological role. Fed. Proc.27, 84–89 (1968).

    Google Scholar 

  • —, Ratnoff, O. D.: Role of Hageman factor in the activation of vasodilator activity in human plasma. Nature (Lond.)192, 180–181 (1961).

    Google Scholar 

  • Wilner, G. D., Nossel, H. L., LeRoy, E. C.: Activation of Hageman factor by collagen. J. clin. Invest.47, 2608–2615 (1968).

    Google Scholar 

  • Wuepper, K. D., Cochrane, C. G.: Plasma prokininogenase: mechanism of activation. Fed. Proc.29, 811 (1970).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmakologisches Institut der Justus Liebig-Universität, Gießen

    Rosemarie Jahrreiss & E. Habermann

Authors
  1. Rosemarie Jahrreiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Habermann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jahrreiss, R., Habermann, E. On the endogenous mechanism of kinin release. Naunyn-Schmiedebergs Arch. Pharmak. 269, 85–100 (1971). https://doi.org/10.1007/BF01422018

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01422018

Key-words

Search

Navigation