Analysis of A2a receptor-deficient mice reveals no significant compensatory increases in the expression of A2b, A1, and A3 adenosine receptors in lymphoid organs

Biochem Pharmacol. 2003 Jun 15;65(12):2081-90. doi: 10.1016/s0006-2952(03)00158-8.


Although recent genetic and pharmacologic in vivo studies of acute inflammation models in mice demonstrated that the cyclic AMP-elevating A2a receptor plays a non-redundant role in protection from excessive acute inflammatory tissue damage and in the down-regulation of proinflammatory cytokine production, it remained to be established whether genetic deficiency of the A2a receptor is accompanied by a compensatory up-regulation of the cAMP-elevating A2b receptor and/or other adenosine receptors. Here, we show that most of the cAMP response to adenosine is abolished in lymphoid tissues of A2a receptor-deficient mice, although some response remains in splenocytes. No significant changes were observed in A2b, A1, and A3 mRNA levels in the thymus or lymph nodes of A2a receptor-deficient mice, but small increases in mRNA expression of these receptors were detected in the spleen. These data suggest that regulation of the expression of A2b, A1, and A3 receptors is not affected significantly by the absence of A2a receptors and may provide further explanation of earlier in vivo observations of increased tissue damage and of longer persistence of proinflammatory cytokines in animals with inactivated A2a receptors.

MeSH terms

  • Adenosine / metabolism
  • Animals
  • Cyclic AMP / metabolism
  • Gene Expression
  • Lymphocytes / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / biosynthesis
  • Receptor, Adenosine A2A
  • Receptor, Adenosine A2B
  • Receptor, Adenosine A3
  • Receptors, Purinergic P1 / biosynthesis*
  • Receptors, Purinergic P1 / deficiency
  • Receptors, Purinergic P1 / genetics
  • Receptors, Purinergic P1 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction


  • RNA, Messenger
  • Receptor, Adenosine A2A
  • Receptor, Adenosine A2B
  • Receptor, Adenosine A3
  • Receptors, Purinergic P1
  • Cyclic AMP
  • Adenosine