Skip to main content
SpringerLink
Log in

Role of calcium in prostaglandin E release induced by bradykinin and the ionophore A 23187

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

  1. 1.

    The role of calcium for PGE release in the activation of phospholipase A2 by bradykinin and the divalent cation ionophore A 23187 was investigated in the isolated perfused rabbit ear.

  2. 2.

    PGE release induced by intra-arterial injection of phospholipase A2 was diminished during perfusion with calcium-free Tyrode's solution and abolished during perfusion with calcium-free, 1 mM EGTA-containing solution.

  3. 3.

    PGE release induced by intra-arterial injection of bradykinin remained unchanged in calcium-free and calcium-free, 1 mM EGTA-containing solution. Addition of 3 mM EGTA to calcium-free perfusion solution reduced PGE release evoked by bradykinin.

  4. 4.

    A 23187, dose-dependently released PGE. The release of PGE induced by a single intra-arterial dose lasted for more than 60 min, in contrast to the much more shortlasting release induced by bradykinin. Infusion of A 23187 caused a steadily increasing release of PGE.

  5. 5.

    A 23187-induced PGE release was not inhibited during perfusion with a calcium-free solution. Addition of 1 mM or 3 mM EGTA to the calcium-free solution reduced PGE release following injection of A 23187.

  6. 6.

    Basal release of PGE remained unchanged during perfusion with calcium-free (without or with EGTA) and “high” (9 mM) calcium-containing solution.

  7. 7.

    The results suggest that bradykinin appears to activate an endogenous phospholipase A2 only to a small part by increasing a transfer of extracellular calcium into the cell. The main part of phospholipase A2-activation by bradykinin remains unexplained. In contrast, A 23187 is assumed to activate a phospholipase A2 mainly by increasing a calcium-influx. The activated phospholipase A2, thereafter, initiates the release of PGE.

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

  • Bartels, J., Kunze, H., Vogt, W., Wille, G.: Prostaglandin: Liberation from and formation in perfused frog intestine. Naunyn-Schmiedebergs Arch. Pharmakol. 266, 199–207 (1970)

    Google Scholar 

  • Brecht, K., Estada, J. A., Götz, A.: Zur Beeinflussung der Gefäßmotorik durch Ca2+- und K+-Ionen. Ein Beitrag zum Tonusproblem? Pflügers Arch. Ges. Physiol. 279, 330–340 (1964)

    Google Scholar 

  • Bülbring, E., Kuriyama, H.: Effects of changes in ionic environment on the action of acetylcholine and adrenaline on the smooth muscle cells of guinea-pig taenia coli. J. Physiol. 166, 59–74 (1963)

    Google Scholar 

  • Butcher, F. R.: The role of calcium and cyclic nucleotides in α-amylase release from slices of rat parotid: studies with the divalent cation ionophore A 23187. Metabolism 24, 409–418 (1975)

    Google Scholar 

  • Casteels, R., Van Breemen, C., Mayer, C. J.: A study of the calcium distribution in smooth muscle cells of the guinea-pig taenia coli using La3+. Arch. Int. Pharmacol. Ther. 199, 193–194 (1972)

    Google Scholar 

  • Cochrane, D. E., Douglas, W. W., Mouri, T., Nakazato, Y.: Calclum and stimulus-secretion coupling in the adrenal medulla: contrasting stimulating effects of the ionophores X-537A and A 23187 on catecholamine output. J. Physiol. (Lond.) 252, 363–378 (1975)

    Google Scholar 

  • Damas, J., Deby, C.: Sur la libération des prostaglandines et de leur précurseurs, par la bradykinine. Arch. Int. Physiol. Biochim. 84, 293–304 (1976)

    Google Scholar 

  • De Haas, G. H., Postema, N. M., Nieuwenhuizen, W., Van Deenen, L. L. M.: Purification and properties of phospholipase A from porcine pancreas. Biochim. Biophys. Acta 159, 103–117 (1968)

    Google Scholar 

  • Derksen, A., Cohen, P.: Pattens of fatty acid release from endogenous substrates by human platelet homogenates and membranes. J. Biol. Chem. 250, 9342–9347 (1975)

    Google Scholar 

  • Devine, E. C., Somlyo, A. V., Somlyo, A. P.: Sarcoplasmic reticulum and mitochondria as cation accumulation sites in smooth muscle. Phil. Trans. R. Soc. Lond. B 265, 17–23 (1973)

    Google Scholar 

  • Easwell, A. H., Pressman, B. C.: Kinetics of transport of divalent cations across sarcoplasmic reticulum vesicles induced by ionophores. Biochem. Biophys. Res. Commun. 49, 292–298 (1972)

    Google Scholar 

  • Ferreira, S. H., Moncada, S., Vane, J. R.: Prostaglandins and the mechanism of analgesia produced by aspirin-like drugs. Br. J. Pharmacol. 49, 86–97 (1973)

    Google Scholar 

  • Flower, R. J., Blackwell, G. J.: The importance of phospholipase A2 in prostaglandin biosynthesis. Biochem. Pharmacol. 25, 285–291 (1976)

    Google Scholar 

  • Fynn, H., Onomakpome, N., Peart, W. S.: The effects of ionophores (A 23187 and RO 2-2985) on renin secretion and renal vasoconstriction. Proc. R. Soc. Lond. B 199, 199–212 (1977)

    Google Scholar 

  • Goldberg, M. R., Chapnick, B. M., Joiner, P. D., Hyman, A. L., Kadowitz, P. J.: Influence of inhibitors of prostaglandin synthesis on venoconstrictor responses to bradykinin. J. Pharmacol. Exp. Ther. 198, 357–365 (1976)

    Google Scholar 

  • Goodfriend, T. L., Levine, L., Fasman, G. D.: Antibodies to bradykinin and angiotensin: A use of carbodiimides in immunology. Science 144, 1344–1346 (1964)

    Google Scholar 

  • Hainaut, K., Desmedt, J. E.: Calcium ionophore A 23187 potentiates twitch and intracellular calcium release in single muscle fibres. Nature 252, 407–408 (1974)

    Google Scholar 

  • Hurwitz, L., Fitzpatrick, D. F., Debbas, G., Landon, E. J.: Localization of calcium pump activity in smooth muscle. Science 179, 384–386 (1973)

    Google Scholar 

  • Ito, S., Nakano, Y., Ohga, A.: The effect of the ionophores X-537A and A 23187 on the noradrenaline output from peripheral adrenergic neurones in the presence of various divalent cations. Br. J. Pharmacol. 62, 91–98 (1978)

    Google Scholar 

  • Jobke, A., Peskar, B. A., Peskar, B. M.: On the specifity of antisera against prostaglandins A2 and E2. FEBS Lett. 37, 192–196 (1973)

    Google Scholar 

  • Juan, H.: Mechanism of action of bradykinin-induced release of prostaglandin E. Naunyn-Schmiedeberg's Arch. Pharmacol. 300, 77–85 (1977)

    Google Scholar 

  • Juan, H., Lembeck, F.: Action of peptides and other algesic agents on paravascular pain receptors of the isolated perfused rabbit ear. Naunyn-Schmiedeberg's Arch. Pharmacol. 283, 151–164 (1974)

    Google Scholar 

  • Juan, H., Lembeck, F.: Release of prostaglandins from the isolated perfused rabbit ear by bradykinin and acetylcholine. Agents and Actions 6, 642–645 (1976a)

    Google Scholar 

  • Juan, H., Lembeck, F.: Bradykinin-induced PGE release: mode of action. Naunyn-Schmiedeberg's Arch. Pharmacol. 294, R7 (1976b)

    Google Scholar 

  • Knapp, H. R., Oelz, O., Roberts, L. J., Sweetman, B. J., Oates, J. A.: Ionophores stimulate prostaglandin and thromboxane biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 74, 4251–4255 (1977)

    Google Scholar 

  • Kunze, H., Vogt, W.: Significance of phospholipase A for prostaglandin formation. Ann. N.Y. Acad. Sci. 180, 123–125 (1971)

    Google Scholar 

  • Kunze, H., Bohn, E., Vogt, E.: Effects of local anaesthetics on prostaglandin biosynthesis in vitro. Biochim. Biophys. Acta 360, 260–269 (1974a)

    Google Scholar 

  • Kunze, H., Nahas, N., Wurl, M.: Phospholipases in human seminal plasma. Biochim. Biophys. Acta 348, 35–44 (1974b)

    Google Scholar 

  • Lands, W. E. M., Samuelsson, B.: Phospholipid precursors of prostaglandins. Biochim. Biophys. Acta 164, 426–429 (1968)

    Google Scholar 

  • Laychock, S. G., Warner, W., Rubin, R. P.: Further studies on the mechanisms controlling prostaglandin biosynthesis in the cat adrenal cortex: the role of calcium and cyclic AMP. Endocrinology 100, 74–81 (1977)

    Google Scholar 

  • Markus, H. B., Ball, E. G.: Inhibition of lipolytic processes in rat adipose tissue by antimalarial drugs. Biochim. Biophys. Acta 187, 486–491 (1969)

    Google Scholar 

  • McGiff, J. C., Terragno, N. A., Malik, K. U., Lonigro, A. J.: Release of a prostaglandin E-like substance from canine kidney by bradykinin. Circ. Res. 31, 36–43 (1972)

    Google Scholar 

  • Moncada, S., Ferreira, S. H., Vane, J. R.: Inhibition of prostaglandin biosynthesis as the mechanism of analgesia of aspirin-like drugs in the dog knee joint. Eur. J. Pharmacol. 31, 250–260 (1975)

    Google Scholar 

  • Needleman, P., Bronson, S. D., Wyche, A., Sivakoff, M., Nicolaou, K. C.: Cardiac and renal prostaglandin I2. J. Clin. Invest. 61, 839–849 (1978)

    Google Scholar 

  • Palmer, M. A., Piper, P. J., Vane, J. R.: Release of rabbit aorta contracting substance (RCS) and prostaglandins induced by chemical or mechanical stimulation of guinea-pig lungs. Br. J. Pharmacol. 49, 226–242 (1973)

    Google Scholar 

  • Peskar, B., Hertting, G.: Release of prostaglandins from isolated cat spleen by angiotensin and vasopresin. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 227–234 (1973)

    Google Scholar 

  • Peskar, B. M., Peskar, B. A.: On the metabolism of prostaglandins by human gastric fundus mucosa. Biochim. Biophys. Acta 424, 430–438 (1976)

    Google Scholar 

  • Pickett, W. C., Cohen, P.: Mechanism of the thrombin-mediated burst in oxygen consumption by human platelets. J. Biol. Chem. 251, 2536–2538 (1976)

    Google Scholar 

  • Pickett, W. C., Jesse, R. L., Cohen, P.: Trypsin-induced phospholipase activity in human platelets. Biochem. J. 160, 405–408 (1976)

    Google Scholar 

  • Pickett, W. C., Jesse, R. L., Cohen, P.: Initiation of phospholipase A2 activity in human platelets by the calcium ion ionophore A 23187. Biochim. Biophys. Acta 486, 209–213 (1977)

    Google Scholar 

  • Reed, P. W., Lardy, H. A.: A 23187: A divalent cation ionophore. J. Biol. Chem. 247, 6970–6977 (1972)

    Google Scholar 

  • Scarpa, A., Baldassare, J., Inesi, G.: The effect of calcium ionophores of fragmented sarcoplasmic reticulum. J. Gen. Physiol. 60, 735–749 (1972)

    Google Scholar 

  • Schroeder, T. E., Strickland, D. L.: Ionophore A 23187, calcium and contractility in frog eggs. Exp. Cell. Res. 83, 139–142 (1974)

    Google Scholar 

  • Somlyo, A. P.: Excitation-contraction coupling in vertebrate smooth muscle. Correlation of ultrastructure with function. Physiologist 15, 338–348 (1972)

    Google Scholar 

  • Vargaftig, B. B.: The pharmacology of slow reacting substance C and of arachidonic acid. Agents and Actions 3, 357–365 (1973)

    Google Scholar 

  • Vargaftig, B. B., Dao Hai, N.: Selective inhibition by mepacrine of the release of “rabbit aorta contracting substance” evoked by the administration of bradykinin. J. Pharm. Pharmacol. 24, 159–161 (1972)

    Google Scholar 

  • Vogt, W., Suzuki, T., Babilli, S.: Prostaglandins in SRS-C and in a darmstoff preparation from frog intestinal dialysates. In: Endogenous substances affecting the myometrium (V. R. Pickles and R. J. Fitzpatrick, eds.). London-Cambridge: University Press 1966

    Google Scholar 

  • Vogt, W., Meyer, U., Kunze, H., Lufft, E., Babilli, S.: Entstehung von SRS-C in der durchströmten Meerschweinchenlunge durch Phospholipase A. Identifizierung mit Prostaglandin. Naunyn-Schmiedeberg's Arch. Pharmak. exp. Path. 262, 124–134 (1969)

    Google Scholar 

  • Vonkeman, H., Van Dorp, D. A.: The action of prostaglandin synthetase on 2-arachidonyl-lecithin. Biochim. Biophys. Acta 164, 430–432 (1968)

    Google Scholar 

  • Wentzell, B., Epand, R. M.: Stimulation of the release of prostaglandins from polymorphonuclear leukocytes by the calcium ionophore A 23187. FEBS Letters 86, 255–258 (1978)

    Google Scholar 

  • Wilkinson, D. I., Walsh, J. T.: Prostaglandin biosynthesis in the epidermis and dermis of young mouse skin, and the effects of calcium and cyclic nucleotides. J. Invest. Dermatol. 68, 210–214 (1977)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für experimentelle und klinische Pharmakologie, Universitätsplatz 4, A-8010, Graz, Austria

    H. Juan

Authors
  1. H. Juan
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This investigation was supported by the Grant No. 3092 from the Fond zur Förderung der wissenschaftlichen Forschung in Österreich

Rights and permissions

Reprints and permissions

About this article

Cite this article

Juan, H. Role of calcium in prostaglandin E release induced by bradykinin and the ionophore A 23187. Naunyn-Schmiedeberg's Arch. Pharmacol. 307, 177–183 (1979). https://doi.org/10.1007/BF00498461

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00498461

Key words

Search

Navigation