Adenosine A(2B) receptors behave as an alternative anchoring protein for cell surface adenosine deaminase in lymphocytes and cultured cells

Adenosine deaminase (ADA) is an enzyme of the purine metabolism that has be en largely considered to be cytosolic. Recently, it has been demonstrated t hat the enzyme appears on the surface of lymphocytes where it interacts wit h the T-cell activation antigen CD26. ADA also appears on the surface of no nlymphoid cells anchored to adenosine A(1) receptors. Here it is demonstrat ed that cell surface ADA in ADA(+)/CD26(-) T lymphocytes anchors to adenosi ne receptors of the A(2B) subtype (A(2B)R). An interaction between A(2B)R a nd cell surface ADA has been demonstrated in transfected Chinese hamster ov ary cells and Jurkat J32 T lymphocytes. This has been proved by coimmunopre cipitation, binding of exogenous ADA to A(2B)R(+) cells, and coimmunolocali zation. The specificity of the interaction has also been demonstrated by th e lack of interaction with other members of the G protein-coupled receptor superfamily. Binding of ADA to A(2B)R increases the affinity of the agonist 5'-N-ethylcarboxamidoadenosine and cAMP production. This effect occurs eve n when ADA devoid of enzyme activity is used. Therefore, in lymphocytes, ce ll surface ADA, apart from degrading extracellular adenosine, regulates tho se actions of adenosine that are mediated via adenosine receptors of the A( 2B) subtype.