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Effect of des arginine9-bradykinin and other bradykinin fragments on the synthesis of prostacyclin and the binding of bradykinin by vascular cells in culture

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Abstract

Bradykinin (BK) fragments, des arg1-BK, des arg1,pro2-BK, des phe8,arg9-BK and des pro7,phe8,arg9-BK were synthesized and along with des arginine9-BK (daBK), tested for their ability to induce prostacyclin synthesis in homogeneous cultures of cells from the calf pulmonary artery. Of the fragments daBK was the only peptide, in addition to bradykinin (BK), to activate the synthesis of prostacyclin (PGI2) and platelet activating factor (PAF) in endothelial cells and PGI2 in fibroblasts and smooth muscle cells. Half-maximal activation of PGI2 synthesis differed with the cell type. The other fragments tested did not directly affect PGI2 synthesis. These fragments also did not inhibit daBK or BK activation of PG synthesis.

BK bound to endothelial cells with a dissociation constant (Kd) of 2.1 nM and a Bmax of 47.9 fmoles/106 cells. The Kd for the binding of BK to smooth muscle cells and fibroblasts was somewhat higher, 4.9 nM and 7.9 nM, respectively. None of the fragments tested, including daBK, altered the binding of BK. Des arg9[leu8]-BK, reported to be a competitive antagonist of the bradykinin B1 receptor, inhibited daBK induced PG of PAF synthesis in endothelial cells but had little effect of BK binding or BK induced PG synthesis. Finally, the BK antagonist [thi5,8, d-phe7]-BK blocked both BK binding and the ability of either BK or daBK to induce PG synthesis, thus substantiating that the binding of these kinins is a step in the activation of PG synthesis.

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Abbreviations

PG:

prostaglandin (E2, I2 etc.)

PAF:

platelet activating factor

HEPES:

N-2-hydoxyethyl-piperazine-N′-2-ethylsulfonic acid

BSA:

bovine serum albumin

HPLC:

high performance liquid chromatography

TLC:

thin layer chromatography

BK:

bradykinin

daBK:

des arg9-bradykinin

Kd :

binding dissociation constant

Bmax :

maximal binding

PLA2 :

phospholipase A2

RIA:

radioimmunoassay

FBS:

fetal bovine serum

pA2 :

negative logarithm of the antagonist concentration that reduces the response to a double dose of the agonist to the response obtained with a single dose

References

  1. R. D. Dyer, J. J. Huttner, S. Y. Tan and R. J. Mulrow,Prostaglandin synthesis by vascular smooth muscle cells is stimulated by bradykinin, prazosin and hydralizine, Prog. Lipid Res.20, 557–560 (1981).

    Article  PubMed  Google Scholar 

  2. S. L. Hong,Effect of bradykinin and thrombin on prostacyclin synthesis in endothelial cells from calf and pig aorta and human umbilical cord vein, Thromb. Res.18, 787–795 (1980).

    Article  PubMed  Google Scholar 

  3. P. M. Vanhoutte,The endothelium and arterial reactivity, J. Mal. Vasc.11, 213–221 (1986).

    PubMed  Google Scholar 

  4. A. Schweizer, R. Brom, M. Glatt and M. A. Bray,Leukotrienes reduce nociceptive responses to bradykinin, Eur. J. Pharmacol.105, 105–112 (1984).

    Article  PubMed  Google Scholar 

  5. T. M. McIntyre, G. A. Zimmerman, K. Satoh and S. M. Prescott,Cultured endothelial cells synthesize both plateletactivating factor and prostacyclin in response to histamine, bradykinin and adenosine triphosphate, J. Clin. Invest.76, 271–280 (1985).

    PubMed  Google Scholar 

  6. F. Marceau, A. Lussier, D. Regoli and J. P. Giroud,Pharmacology of kinin: Their relevance to tissue injury and inflammation, Gen. Pharmacol.14, 209–229 (1983).

    PubMed  Google Scholar 

  7. S. L. Hong and D. Deykin,Activation of phospholipase A 2 in pig aortic endothelial cells synthesizing prostacyclin, J. Biol. Chem.257, 7151–7154 (1982).

    PubMed  Google Scholar 

  8. C. K. Derian and M. A. Moskowitz,Polyphosphoinositide hydrolysis in endothelial cells and carotid artery segments, J. Biol. Chem.261, 3831–3837 (1986).

    PubMed  Google Scholar 

  9. A. R. Whorton, C. E. Willis, R. S. Kent and S. L. Young,The role of calcium in the regulation of prostacyclin synthesis by porcine aortic endothelial cells, Lipids19, 17–24 (1984).

    PubMed  Google Scholar 

  10. J. V. Pierce,Purification of mammalian kallikreins, kininogens and kinins, In:Handbook of Experimental Pharmacology, vol. 25, 21–51 (Ed. E. G. Erdos), Springer-Verlag, Berlin (1970).

    Google Scholar 

  11. D. Regoli and J. Barabe,Pharmacology of bradykinin and related kinins. Pharmacol. Rev.32, 1–46 (1980).

    PubMed  Google Scholar 

  12. E. T. Whalley, H. Fritz and R. Geiger,Kinin receptors and angiotensin converting enzyme in rabbits basilar arteries, Naunyn-Schmied. Arch. Pharmacol.324, 296–301 (1983).

    Article  Google Scholar 

  13. R. H. Goldstein and M. Wall,Activation of protein formation and cell division by bradykinin and des-arg-bradykinin, J. Biol. Chem.254, 9263–9268 (1984).

    Google Scholar 

  14. L. Taylor and P. Polgar,Stimulation of prostaglandin synthesis by ascorbic acid via hydrogen peroxide formation, Prostaglandins19, 693–700 (1980).

    Article  PubMed  Google Scholar 

  15. M. Menconi, G. Hahn and P. Polgar,Prostaglandin synthesis by cells comprising the calf pulmonary artery, J. Cell. Physiol.120, 163–168 (1984).

    Article  PubMed  Google Scholar 

  16. K. S. Weinberg, W. H. J. Douglas, D. R. MacNamee, J. J. Lanzillo and B. L. Fanburg,Angiotensin I converting enzyme localization in cultured fibroblasts by immunofluorescence, In vitro 18, 400–406 (1982).

    PubMed  Google Scholar 

  17. B. Farris, L. L. Salcedo, V. Cook, L. Johnson, J. A. Foster and C. Franzblau,The synthesis of connective tissue protein in smooth muscle cells, Biochim. Biophys Acta418, 93–103 (1976).

    PubMed  Google Scholar 

  18. R. Mayne, M. S. Vail, E. J. Miller, S. H. Blose and S. Chacko,Collagen polymorphism in cell cultures derived from guinea pig aortic smooth muscle: Comparison with three populations of fibroblasts, Arch. Biochem. Biophys.181, 462–469 (1977).

    Article  PubMed  Google Scholar 

  19. M. L. Blank and F. Snyder,Improved high-performance liquid chromatographic method for isolation of platelet activating factor from other phospholipids, J. Chromatogr.273, 415–420 (1983).

    PubMed  Google Scholar 

  20. C. Heinsohn, P. Polgar, J. Fishman and L. Taylor,The effect of bovine serum albumin on the synthesis of prostaglandin and incorporation of [3 H]acetate into platelet-activation factor, Arch. Biochem. Biophys.257, 251–258 (1987).

    Article  PubMed  Google Scholar 

  21. A. A. Roscher, V. C. Manganiello, C. L. Jelsema and J. Moss,Receptors for bradykinin in intact cultured human fibroblasts. Identification and characterization by direct binding study, J. Clin Invest.72, 626–635 (1983).

    PubMed  Google Scholar 

  22. R. B. Meerifield,Solid phase peptide synthesis. II The synthesis of bradykinin, J. Am. Chem. Soc.86, 304–305 (1964).

    Article  Google Scholar 

  23. H. O. Shield,pA, a new scale for the measurement of drug antagonism, Brit. J. Pharmacol.2, 189–206 (1947).

    Google Scholar 

  24. G. Scatchard,The attractions of proteins for small molecules and ions, Ann. N.Y. Acad. Sci.51, 660–672 (1949).

    Google Scholar 

  25. A. Hassid, N. Pidikiti and D. Gamero,Effects of vasoactive peptides on cytosolic calcium in cultured mesangial cells, Am. J. Physiol.251, F1018-F1028 (1986).

    PubMed  Google Scholar 

  26. D. C. Regoli, F. Marceau and J. Lavigne,Induction of B 1-receptors for kinins in the rabbit by a bacterial lipopolysaccharide, Eur. J. of Pharm.71, 105–115 (1981).

    Article  Google Scholar 

  27. D. Regoli, J. Barabe and W. K. Park, Receptors of bradykinin in rabbit aortae, Can. J. Physiol. Pharmacol.55, 855–867 (1977).

    PubMed  Google Scholar 

  28. P. M. Vanhoutte and T. J. Rimele,Role of the endothelium in the control of vascular smooth muscle function, J. de Physiol. (Paris)78, 681–686 (1982/1983).

    Google Scholar 

  29. P. D. Cherry, R. F. Furchgott and J. V. Zawadski,Role of endothelial cells in relaxation of isolated arteries by bradykinin, Proc. Nat. Acad. Sci. USA79, 2106–2110 (1982).

    PubMed  Google Scholar 

  30. W. S. Webster, S. P. Bishop and J. C. Geer,Experimental aortic intimal thickening II. Endothelialization and permeability, Am. J. Pathol.76, 265–284 (1974).

    PubMed  Google Scholar 

  31. L. Churchill and P. E. Ward,Relaxation of isolated mesenteric arteries by des-Arg 9 t-bradykinin stimulation of B 1 receptors, Eur. J. Pharmacol.130, 11–18 (1986).

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Boston University School of Medicine, 80 East Concord St., 02118, Boston, MA

    M. Cahill, J. B. Fishman & P. Polgar

  2. The ENR Memorial Veterans Administration Hospital, 01730, Bedford, MA

    J. B. Fishman

Authors
  1. M. Cahill
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  2. J. B. Fishman
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  3. P. Polgar
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Additional information

This work was supported by NIH grants AG05007, HL25776 and HL07035.

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Cahill, M., Fishman, J.B. & Polgar, P. Effect of des arginine9-bradykinin and other bradykinin fragments on the synthesis of prostacyclin and the binding of bradykinin by vascular cells in culture. Agents and Actions 24, 224–231 (1988). https://doi.org/10.1007/BF02028275

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