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Dual actions of adenosine on rat peritoneal mast cells

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Summary

The effects of adenosine and its analogues on cAMP-responses and histamine release of rat peritoneal mast cells were investigated. The adenosine analogue 5′-N-ethylcarboxamidoadenosine (NECA') activates the adenylate cyclase of the mast cell membranes and elevates the cAMP-levels of the intact mast cells. Both effects are antagonized by methylxanthines, suggesting that they are mediated via an A2 adenosine receptor. Adenosine and its analogues enhance the release of histamine from these cells, when the release is stimulated either by the calcium ionophore A 23187 or by concanavalin A. However, this effect is not antagonized by theophylline or 8-phenyltheophylline. In contrast, it is antagonized by the adenosine uptake blockers S-(p-nitrobenzyl)-6-thioinosine (NBTI) and S-(p-nitrobenzyl)-6-thioguanosine (NBTG). It is concluded that adenosine has two different effects on mast cells: it activates adenylate cyclase via an A2 adenosine receptor, and it enhances histamine release via an action at an intracellular site.

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Abbreviations

NECA:

5′-N-ethylcarboxamidoadenosine

NBTI:

S-(p-nitrobenzyl)-6-thioinosine

NBTG:

S-(p-nitrobenzyl)-6-thioguanosine

PIA:

N6-phenylisopropyladenosine

Con A:

concanavalin A

References

  • Anton AH, Sayre DF (1969) A modified fluorometric procedure for tissue histamine and its distribution in various animals. J Pharmacol Exp Ther 166:285–292

    Google Scholar 

  • Burt DS, Stanworth DR (1983) The effect of ribose and purine modified adenosine analogues on the secretion of histamine from rat mast cells induced by ionophore A 23187. Biochem Pharmacol 32:2729–2732

    Google Scholar 

  • Cheng YC, Prusoff WH (1973) Relationship between the inhibition constant (K i) and the concentration of inhibitor which causes 50% inhibition (IC50) of an enzymatic reaction. Biochem Pharmacol 22:3099–3108

    Article  CAS  PubMed  Google Scholar 

  • Church MK, Holgate ST, Hughes PJ (1983) Adenosine inhibits and potentiates IgE-dependent histamine release from human basophils by an A2-receptor mediated mechanism. Br J Pharmacol 80:719–726

    Google Scholar 

  • Church MK, Hughes PJ, Vardey CJ (1986) Studies on the receptor mediating cyclic AMP-independent enhancement by adenosine of IgE-dependent mediator release from rat mast cells. Br J Pharmacol 87:233–242

    Google Scholar 

  • Church MK, Hughes PJ (1985) Adenosine potentiates immunological histamine release from rat mast cells by a novel cyclic AMP-independent cell-surface action. Br J Pharmacol 85:3–5

    Google Scholar 

  • Delmich K, Eichelberg D, Schmutzler W (1985) The effects of adenosine and of some adenosine analogues on the concanavalin A- or acetylcholine-induced histamine release from human adenoidal mast cells. Agents Actions 16:141–143

    Google Scholar 

  • Foreman J (1980) Receptor-secretion coupling in mast cells. Trends Pharmacol Sci 1:460–462

    Google Scholar 

  • Fredholm BB (1980) Are methylxanthine effects due to antagonism of endogenous adenosine? Trends Pharmacol Sci 1:129–132

    Google Scholar 

  • Harper JF, Brooker G (1975) Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2′O acetylation by acetic anhydride in aqueous solution. J Cyclic Nucleotide Res 1:207–218

    Google Scholar 

  • Holgate ST, Lewis RA, Austen KF (1980) Role of adenylate cyclase in immunologic release of mediators from rat mast cells: Agonist and antagonist effects of purine- and ribose-modified adenosine analogs. Proc Natl Acad Sci USA 77:6800–6804

    Google Scholar 

  • Hüttemann E, Ukena D, Lenschow V, Schwabe U (1984) Ra adenosine receptor in human platelets. Naunyn-Schmiedeberg's Arch Pharmacol 325:226–233

    Google Scholar 

  • Hughes PJ, Holgate ST, Church MK (1984) Adenosine inhibits and potentiates IgE-dependent histamine release from human lung mast cells by an A2-purinoceptor mediated mechanism. Biochem Pharmacol 33:3847–3852

    Google Scholar 

  • Hughes PJ, Church MK (1986) Separate purinoceptors mediate enhancement by adenosine of concanavalin A-induced mediator release and the cyclic AMP response in rat mast cells. Agents Actions 18:81–84

    Google Scholar 

  • Jakobs KH, Saur W, Schultz G (1976) Reduction of adenylate cyclase activity in lysates of human platelets by the alpha-adrenergic component of epinephrine. J Cyclic Nucleotide Res 2:381–392

    Google Scholar 

  • Kolassa N, Pfleger K (1975) Adenosine uptake by erythrocytes of man, rat and guinea-pig and its inhibition by hexobendine and dipyridamole. Biochem Pharmacol 24:154–156

    Google Scholar 

  • Leoutsakos A, Pearce FL (1986) The effect of adenosine and its analogues on cyclic AMP changes and histamine secretion from rat peritoneal mast cells stimulated by various ligands. Biochem Pharmacol 35:1373–1379

    Google Scholar 

  • Leoutsakos A, Truneh A, Pearce FL (1985) Role of cyclic AMP in the induction of histamine secretion from mast cells. Agents Actions 16:126–128

    Google Scholar 

  • Lohse MJ, Lenschow V, Schwabe U (1984) Two affinity states of Ri adenosine receptors in brain membranes: Analysis of guanine nucleotide and temperature effects on radioligand binding. Mol Pharmacol 26:1–9

    Google Scholar 

  • Lohse MJ, Klotz K-N, Jakobs KH, Schwabe U (1985) Barbiturates are selective antagonists at A1 adenosine receptors. J Neurochem 45:1761–1770

    Google Scholar 

  • Lohse MJ, Klotz K-N, Schwabe U (1986) Agonist photoaffinity labelling of A1 adenosine receptors: Persistent activation reveals spare receptors. Mol Pharmacol 30:403–409

    Google Scholar 

  • Londos C, Cooper DMF, Wolff J (1980) Subclasses of external adenosine receptors. Proc Natl Acad Sci USA 77:2551–2554

    Google Scholar 

  • Marone G, Findlay SR, Lichtenstein LW (1979) Adenosine receptor on human basophils: Modulation of histamine release. J Immunol 123:1473–1477

    Google Scholar 

  • Marquardt DL, Parker CW, Sullivan TJ (1978) Potentiation of mast cell mediator release by adenosine. J Immunol 120:871–878

    Google Scholar 

  • Marquardt DL, Gruber HE, Wasserman SI (1984) Adenosine release from stimulated mast cells. Proc Nail Acad Sci USA 81:6192–6196

    Google Scholar 

  • May CD, Lyman M, Alberto R, Chang J (1970) Procedures for immunochemical study of histamine release from leucocytes with small volume of blood. J Allergy 46:12–20

    Google Scholar 

  • Nakamura T, Ui M (1985) Simultaneous inhibitions of inositol lipid breakdown, arachidonic acid release, and histamine secretion in mast cells by islet-activating protein, pertussis toxin. J Biol Chem 260:3584–3593

    Google Scholar 

  • Nemeth A, Röhlich P (1980) Rapid separation of rat peritoneal mast cells with Percoll. Eur J Cell Biol 20:272–275

    Google Scholar 

  • Paterson ARP, Jakobs ES, Harley ER, Fu N-W, Robins MJ, Cass CE (1983) Inhibition of nucleoside transport. In: Berne RM, Rall TW, Rubio R (eds) Regulatory function of adenosine. Martinus Nijhoff, Den Haag, pp 203–220

    Google Scholar 

  • Schwabe U, Ukena D, Lohse MJ (1985) Xanthine derivatives as antagonists at A1 and A2 adenosine receptors. Naunyn-Schmiedeberg's Arch Pharmacol 330:212–221

    Google Scholar 

  • Shore PA, Burkhalter A, Cohn VH (1959) A method for the fluorometric assay of histamine in tissues. J Pharmacol Exp Ther 127:182–186

    Google Scholar 

  • Sydbom A, Fredholm B, Uvnäs B (1981) Evidence against a role of cyclic nucleotides in the regulation of anaphylactic histamine release in isolated mast cells. Acta Physiol Scand 112:47–56

    Google Scholar 

  • Van Calker D, Müller M, Hamprecht B (1978) Adenosine inhibits the accumulation of cyclic AMP in cultured brain cells. Nature (Lond) 276:839–841

    Google Scholar 

  • Vardey CJ, Skidmore IF (1985) Characterization of the adenosine receptor responsible for the enhancement of mediator release from rat mast cells. In: Stone TW (ed) Purines: Pharmacology and physiological roles. VCH Verlagsgesellschaft, Weinheim, p 175

    Google Scholar 

  • Verma A, Marangos PJ (1985) Nitrobenzylthioinosine binding in brain: An interspecies study. Life Sci 36:283–290

    Google Scholar 

  • Walseth TF, Johnson RA (1979) The enzymatic preparation of [α-32P]nucleoside triphosphates, cyclic [32P]AMP and cyclic [32P]GMP. Biochem Biophys Acta 526:11–31

    Google Scholar 

  • Welton AF, Simko BA (1980) Regulatory role of adenosine in antigen-induced histamine release from the lung tissue of actively sensitized guinea pigs. Biochem Pharmacol 29:1085–1092

    Google Scholar 

  • White JR, Ishizaka T, Ishizaka K, Sha'afi RI (1984) Direct demonstration of increased intracellular concentration of free calcium as measured by quin-2 in stimulated rat peritoneal mast cell. Proc Natl Acad Sci USA 81:3978–3982

    Google Scholar 

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Authors and Affiliations

  1. Pharmakologisches Institut der Universität Heidelberg, Im Neuenheimer Feld 366, D-6900, Heidelberg, Federal Republic of Germany

    Martin J. Lohse, Klaus Maurer, Hans-Peter Gensheimer & Ulrich Schwabe

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  1. Martin J. Lohse
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  2. Klaus Maurer
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  3. Hans-Peter Gensheimer
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  4. Ulrich Schwabe
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Lohse, M.J., Maurer, K., Gensheimer, HP. et al. Dual actions of adenosine on rat peritoneal mast cells. Naunyn-Schmiedeberg's Arch Pharmacol 335, 555–560 (1987). https://doi.org/10.1007/BF00169124

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  • DOI: https://doi.org/10.1007/BF00169124

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