Inhibition by adenosine of histamine and leukotriene release from human basophils

Peter T. Peachell, Lawrence M. Lichtenstein, Robert P. Schleimer*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Adenosine inhibited the release of histamine and leukotriene C4 (LTC4) from immuno-logically-activated basophils in a dose-dependent manner. Structural congeners of adenosine also attenuated the elaboration of these two mediators from stimulated basophils and a rank order of potency for the inhibition was observed following the sequence 2-chloroadenosine ≥ N-methylcarbox-amidoadenosine (NECA) > adenosine ≥ R-phenylisopropyladenosine (R-PIA) ≥ S-PIA. These same nucleosides modulated the generation of LTC4 more potently than the release of histamine. A number of methylxanthines, which are antagonists of cell surface adenosine receptors, reversed the inhibition by adenosine and its congeners of the release of both histamine and LTC4 to varying extents. Dipy-ridamole and nitrobenzylthioinosine (NBTI), agents that block the intracellular uptake of adenosine, antagonized the inhibition of histamine release by adenosine (and 2-chloroadenosine) but failed to reverse the attenuation of LTC4 generation by the nucleoside. These same uptake blockers were unable to antagonize the inhibitory effects of NECA on either histamine or LTC4 release. In purified basophils, NECA and R-PIA, and in that order of decreasing reactivity, increased total cell cyclic adenosine monophosphate (cAMP) levels and inhibited the stimulated release of mediators. In total, these results suggest that the basophil possesses a cell surface adenosine receptor which, on the basis of both pharmacological and biochemical criteria, most closely conforms to an A2/Ra-like receptor. However, in addition to an interaction at the cell surface, studies with agents that block the intracellular uptake of adenosine suggest that the nucleoside may also exert intracellular effects when countering the release of histamine (but not LTC4).

Original languageEnglish (US)
Pages (from-to)1717-1725
Number of pages9
JournalBiochemical Pharmacology
Volume38
Issue number11
DOIs
StatePublished - Jun 1 1989

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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