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Inflammation Research

, Volume 46, Issue 5, pp 180–184 | Cite as

Adenosine A3 receptors promote degranulation of rat mast cells both in vitro and in vivo

  • J. J. Reeves
  • C. A. Jones
  • M. J. Sheehan
  • C. J. Vardey
  • C. J. Whelan

Abstract.

Objective: To investigate the effects of adenosine receptor agonists and antagonists on 5-HT release from rat isolated pleural mast cells and on plasma protein extravasation in the skin of conscious rats.¶In vitro Methods: Rat isolated pleural mast cells were loaded with [14C] 5-HT, sensitised with mouse monoclonal anti-DNP and then challenged with human serum albumin-DNP. DNP-stimulated 5-HT release from mast cells was determined.¶In vivo Methods: Rats, loaded intravenously with [125I] human serum albumin, were injected intradermally with adenosine agonists at sites on the back. 30 min later plasma protein extravasation at each injection site was determined.¶Results: In isolated mast cells, each adenosine agonist enhanced DNP-induced 5-HT release, N6-(3-iodobenzyl)-5-(N-methyl-carboxamidoadenosine), (IB-MECA), being the most potent agonist. The adenosine A1/A2 antagonist, 8-phenyltheophylline (8-PT), had no effect on the response to IB-MECA. In contrast, 3-(4-amino-iodobenzyl)-8-[4-[[[carboxy]methyl]oxy]phenyl]-1-propylxanthine, (I-ABOPX), inhibited (pA2 6.2) the IB-MECA responses. In the skin of conscious rats, intradermal IB-MECA produced a marked plasma protein extravasation (PPE) which was mimicked by N6-2-(4-aminophenyl)-ethyladenosine (APNEA). The PPE produced by IB-MECA was not affected by either 8-PT or CGS15943A, but was virtually abolished by cyproheptadine and in rats pre-treated with Compound 48/80.¶Conclusions: These results indicate that stimulation of adenosine A3 receptors both enhances degranulation in vitro and directly produces degranulation of rat mast cells in vivo.

Key words: Rat mast cells — Degranulation — Adenosine A3 receptors 

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Copyright information

© Birkhäuser Verlag, Basel, 1997

Authors and Affiliations

  • J. J. Reeves
    • 1
  • C. A. Jones
    • 1
  • M. J. Sheehan
    • 1
  • C. J. Vardey
    • 1
  • C. J. Whelan
    • 1
  1. 1.Receptor Pharmacology Unit, Glaxo Wellcome Research & Development Ltd, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UKGB

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