Premium
Regulation of adenosine receptor engagement by ecto‐adenosine deaminase
Author(s) -
Hashikawa Tomoko,
Hooker Scott W.,
Maj Jerzy G.,
KnottCraig Christopher J.,
Takedachi Masahide,
Murakami Shinya,
Thompson Linda F.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0011fje
Subject(s) - adenosine deaminase , adenosine , adenosine a2b receptor , extracellular , adenosine receptor , adenosine a3 receptor , microbiology and biotechnology , transfection , receptor , inosine , biology , chemistry , biochemistry , agonist , gene
Adenosine deaminase (ADA) can localize to the cell surface through its interaction with CD26. Using CD26‐transfected cells, we demonstrate that cell surface ADA (ecto‐ADA) can regulate adenosine receptor engagement by degrading extracellular adenosine (Ado) to inosine. This ability was dependent upon CD26 expression, the extent of CD26 saturation with ecto‐ADA, and the kinetics of the cAMP response. Thus, the cAMP response was markedly decreased when CD26‐transfected cells were incubated with an exogenous source of ADA to increase ecto‐ADA expression. The ability of ecto‐ADA to inhibit the cAMP response was demonstrated by treatment with the specific ADA inhibitor 2′‐deoxycoformycin. This inhibited the ability of ecto‐ADA to degrade Ado and increased the cAMP response. Although CD26 expression on human thymocytes was low compared with that of CD26‐transfected cells, it was saturated with ecto‐ADA. When thymocytes incubated at high densities (to mimic the situation in tissues) were exposed to exogenous adenosine, the cAMP response was dramatically decreased by ecto‐ADA. We conclude that ecto‐ADA has the potential to regulate adenosine receptor‐mediated cAMP responses in vivo in tissues with CD26 + cells and sufficient cell death caused by apoptosis or inflammation to provide a source of ADA to bind to CD26.