Regulation of adenosine receptor engagement by ecto-adenosine deaminase.
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.
Hashikawa
Tomoko
T
Oklahoma Medical Research Foundation, Immunobiology and Cancer Research Program, Oklahoma City, Oklahoma, USA.
Hooker
Scott W
SW
Maj
Jerzy G
JG
Knott-Craig
Christopher J
CJ
Takedachi
Masahide
M
Murakami
Shinya
S
Thompson
Linda F
LF
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D014162:Transfection
D018047:Receptors, Purinergic P1; D000242:Cyclic AMP; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase; D000241:Adenosine