Studies on the receptor mediating cyclic AMP-independent enhancement by adenosine of IgE-dependent mediator release from rat mast cells

Br J Pharmacol. 1986 Jan;87(1):233-42. doi: 10.1111/j.1476-5381.1986.tb10176.x.


Adenosine produced a concentration-related enhancement of antigen-induced 5-hydroxytryptamine (5-HT) release from rat serosal mast cells. This potentiation was maximal following the simultaneous addition of adenosine with antigen. Enhancement of 5-HT release was accompanied by potentiation of the adenosine 3':5'-cyclic monophosphate (cyclic AMP) response to challenge. The cyclic AMP response, which was antagonized by 8-phenyltheophylline, was characterized as an A2-purinoceptor-mediated effect by the use of 5'-N-ethylcarboxamideadenosine (NECA) and L-N6-phenylisopropyladenosine (L-PIA). Enhancement of 5-HT release, conversely, was not blocked by 8-phenyltheophylline suggesting it to be mediated by a cyclic AMP-independent mechanism. The effect of adenosine on 5-HT release was not reduced by the inhibition of the facilitated uptake of adenosine with dipyridamole, hexobendine or p-nitrobenzylthioguanosine, therefore, suggesting it to be mediated by a cell surface receptor. The receptor mediating enhancement of 5-HT does not appear to belong to the P2-purinoceptor subtype as adenosine was more potent than both adenosine monophosphate (AMP) and adenosine diphosphate (ADP) and alpha, beta-methylene ATP was inactive. Furthermore, the effects of AMP were blocked by alpha, beta-methylene ADP, which inhibits the conversion of AMP to adenosine. Adenosine, NECA, L- and D-PIA were all of equal potency in enhancing 5-HT release. Inosine and 3-deazaadenosine were also active. The rank order of potency of these adenosine analogues is not consistent with an effect at A1- or A2-purinoceptors. There appear to be two adenosine receptors on rat mast cells, an A2-purinoceptor which stimulates adenylate cyclase and a separate purinoceptor, stimulation of which produces enhancement of mediator release by an unknown mechanism. The effects mediated by these receptors appear to be independent of each other.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Adenine Nucleotides / pharmacology
  • Adenosine / pharmacology*
  • Animals
  • Cyclic AMP / physiology*
  • Dose-Response Relationship, Drug
  • Immunoglobulin E / immunology*
  • In Vitro Techniques
  • Male
  • Mast Cells / metabolism*
  • Phenylisopropyladenosine / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Cell Surface / analysis
  • Receptors, Cell Surface / drug effects*
  • Receptors, Purinergic
  • Serotonin / metabolism*
  • Tachyphylaxis / drug effects
  • Theophylline / analogs & derivatives
  • Theophylline / pharmacology
  • Time Factors
  • Tubercidin / pharmacology


  • Adenine Nucleotides
  • Receptors, Cell Surface
  • Receptors, Purinergic
  • 3-deazaadenosine
  • Phenylisopropyladenosine
  • Serotonin
  • Immunoglobulin E
  • 9-(2-hydroxy-3-nonyl)adenine
  • Theophylline
  • Cyclic AMP
  • 8-phenyltheophylline
  • Adenine
  • Adenosine
  • Tubercidin
  • 1-Methyl-3-isobutylxanthine