Nucleosides such as
adenosine (
Ado) influence nearly every aspect of physiology and pathophysiology. Extracellular
nucleotides liberated at local sites of
inflammation are metabolized through regulated phosphohydrolysis by a series of ecto-
nucleotidases including ectonucleoside
triphosphate diphosphohydrolase-1 (CD39) and
ecto-5'-nucleotidase (CD73), found on the surface of a variety of cell types. Once generated,
Ado is made available to bind and activate one of four
G protein-coupled
Ado receptors. Recent in vitro and in vivo studies implicate
Ado in a broad array of tissue-protective mechanisms that provide new insight into
adenosine actions. Studies in cultured cells and murine tissues have indicated that
Ado receptors couple to novel posttranslational
protein modifications, including
Cullin deneddylation, as a new anti-inflammatory mechanism. Studies in
Ado receptor-null mice have been revealing and indicate a particularly important role for the
Ado A2B receptor in animal models of intestinal
inflammation. Here, we review contributions of
Ado to cell and tissue stress responses, with a particular emphasis on the gastrointestinal mucosa.