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Kinins IV pp 571-575 | Cite as

Action and Metabolism of Des(Arg)kinins in Mesenteric Arteries

  • Laurie Churchill
  • John C. McGiff
  • Patrick E. Ward
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 198A)

Summary

Kallidin and bradykinin can be hydrolyzed at their C-termini to produce des(Arg10)kallidin and des(Arg9)bradykinin respectively. These des(Arg)kinins, previously thought to be biologically inactive, are now known to have potent effects on B1 receptors. Although stimulation of B1 receptors has been reported to produce peripheral vasodepressor responses in certain experimental states, only constriction has been reported in isolated vessels (i. e., rabbit aorta, basilar artery, mesenteric vein). In the present study, we have investigated the biologic activity of desg(Arg) kinins on a peripheral resistance vessel (rabbit mesenteric artery). We found that des(Arg)bradykinin relaxes mesenteric arteries, and that its potency relative to kallidin and bradykinin is consistent with the presence of B1 receptors. Further, intact mesenteric arteries, and a plasma membrane fraction purified from these arteries, contained a carboxypeptidase activity which was capable of producing des(Arg)kinins from both kallidin and bradykinin. Thus, these data demonstrate that the vasculature has the enzymatic capacity to form B1 kinins, and that stimulation of B1 receptors in resistance vessels can be associated with peripheral vasodilation.

Keywords

Mesenteric Artery Basilar Artery Rabbit Aorta Plasma Membrane Fraction Kinin Receptor 
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.

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References

  1. 1.
    Erdos, E.G., ed.: Handbook of Experimental Pharmacology, Vol 25 (Suppl. I ), Springer-Verlag, Heidelberg (1979).Google Scholar
  2. 2.
    Soffer, R.L.: Angiotensin converting enzyme and the regulation of vasoactive peptides. Ann. Rev. Biochem. 45: 73–94 (1976).PubMedCrossRefGoogle Scholar
  3. 3.
    Erdos, E.G.: Kininases. In: Handbook of Experimental Pharmacology, ed. by E.G. Erdos. Springer-Verlag, Heidelberg. Vol. 25 (Suppl. I), pp. 427–487 (1979).Google Scholar
  4. 4.
    Plummer, T.H. and Ryan, T.J.: A potent mercapto-by-product analogue inhibitor for human carboxypeptidase N. Biochem. Biophys. Res. Commun. 98: 448–454 (1981).CrossRefGoogle Scholar
  5. 5.
    Levin, Y., Skidgel, R.A. and Erdos, E.G.: Isolation and characterization of the submits of human plasma carboxypeptidase N (kininase I). Proc. Natl. Acad. Sci. U.S.A. 79: 4618–4622 (1982).PubMedCrossRefGoogle Scholar
  6. 6.
    Regoli, D. and Barabe, J.: Pharmacology of bradykinin and related kinins. Pharmacol. Rev. 32: 1–46 (1980).PubMedGoogle Scholar
  7. 7.
    Barabe, J., Marceau, F., Theriault, B., Drovin, J.N. and Regoli, D.: Cardiovascular actions of kinins in the rabbit. Can. J. Physiol. Pharmacol. 57: 78–91 (1979).PubMedCrossRefGoogle Scholar
  8. 8.
    Gaudreau, P., Barabe, J., St.-Pierre, S. and Regoli, D.: Pharmacological studies of kinins in venous smooth muscles. Can. J. Physiol. Pharmacol. 59: 371–379 (1981).PubMedCrossRefGoogle Scholar
  9. 9.
    Marceau, F., Lussier, A., Regoli, D. and Giroud, J.P.: Pharmacology of kinins: Their relevance to tissue injury and inflammation. Gen. Pharmacol. 14: 209–229 (1983).PubMedCrossRefGoogle Scholar
  10. 10.
    Regoli, D., Barabe, J. and Park, W.K.: Receptors for bradykinin in rabbit aorta. Can. J. Physiol. Pharmacol. 55s 855–867 (1977).PubMedCrossRefGoogle Scholar
  11. 11.
    Marceau, F., Barabe, J., St.-Pierre, S. and Regoli, D.: Kinin receptors in experimental inflammation. Can. J. Physiol. Pharmacol. 58: 536–542 (1980).PubMedCrossRefGoogle Scholar
  12. 12.
    Whalley, E.T., Fritz, H. and Greiger, R.: Kinin receptors and angiotensin converting enzyme in rabbit basilar arteries. Naunym- Schmiedeberg’s Arch. Pharmacol. 324: 296–301 (1983).Google Scholar
  13. 13.
    Regoli, D., Marceau, F. and Barabe, J.: De novo formation of vascular receptors for bradykinin. Can. J. Physiol. Pharmacol. 56: 674–677 (1978).PubMedCrossRefGoogle Scholar
  14. 14.
    Regoli, D., Marceau, F. and Lavigne, J.: Induction of B1-receptors for kinins in the rabbit by a bacterial lipopolysaccharide. Eur. J. Pharmacol. 71: 105–115 (1981).PubMedCrossRefGoogle Scholar
  15. 15.
    Ward, P.E.: Immunoelectrophoretic analysis of vascular, membrane bound angiotensin I converting enzyme, aminopeptidase M, and dipeptidyl (amino) peptidase IV. Biochem. Pharmacol. 33: 3183–3193 (1984).PubMedCrossRefGoogle Scholar
  16. 16.
    Juillerat-Jeanneret, L., Roth, M. and Bargetizi, J.: Some properties of porcine carboxypeptidase N. Hoppe-Seyler1s Z. Physiol. Chem. 363: 51–58 (1982).CrossRefGoogle Scholar
  17. 17.
    Palmieri, F.E., Petrelli, J.J. and Ward, P.E.: Vascular, plasma membrane aminopeptidase M: Metabolism of vasoactive peptides. Biochem. Pharmacol, (in press).Google Scholar
  18. 18.
    Toennies, G. and Kolb, J.J.: Techniques and reagents for paper chromatography. Anal. Chem. 23: 823–826 (1951).CrossRefGoogle Scholar
  19. 19.
    Lawton, W.J., Proud, D., Freeh, M.E., Pierce, J.V., Keiser, H.R. and Pisano, J.J.: Characterization and origin of immunoreactive glandular kallikrein in rat plasma. Biochem. Pharmacol. 30: 1731–1737 (1981).PubMedCrossRefGoogle Scholar
  20. 20.
    Scicli, A.G., Orstavik, T.B., Rabbito, S.F., Murray, R.D. and Carretero, O.A.: Blood kinins after sympathetic nerve stimulation of the rat submandibular gland. Hypertension. 5: (Suppl. I): I-101-I-106 (1983).Google Scholar
  21. 21.
    Nolly, H. and Lama, M.C.: Vascular kallikrein: a kallikrein-like enzyme present in vascular tissue of the rat. Clin. Sci. 63: 249s–251s (1982).Google Scholar
  22. 22.
    Ryan, U.S. and Ryan, J.W.: Endothelial cells and inflammation. Clin. Lab. Med. 3: 577–599 (1983).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Laurie Churchill
    • 1
  • John C. McGiff
    • 1
  • Patrick E. Ward
    • 1
  1. 1.Department of PharmacologyNew York Medical CollegeValhallaUSA

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