Abstract
Four adenosine receptors have been cloned and characterized from several
mammalian species. The receptors are named adenosine A(1), A(2A),
A(2B), and A(3). The A(2A) and A(2B) receptors preferably interact
with members of the G(s) family of G proteins and the A(1) and A(3)
receptors with G(i/o) proteins. However, other G protein interactions
have also been described. Adenosine is the preferred endogenous agonist
at all these receptors, but inosine can also activate the A(3) receptor.
The levels of adenosine seen under basal conditions are sufficient
to cause some activation of all the receptors, at least where they
are abundantly expressed. Adenosine levels during, e.g., ischemia
can activate all receptors even when expressed in low abundance.
Accordingly, experiments with receptor antagonists and mice with
targeted disruption of adenosine A(1), A(2A), and A(3) expression
reveal roles for these receptors under physiological and particularly
pathophysiological conditions. There are pharmacological tools that
can be used to classify A(1), A(2A), and A(3) receptors but few drugs
that interact selectively with A(2B) receptors. Testable models of
the interaction of these drugs with their receptors have been generated
by site-directed mutagenesis and homology-based modelling. Both agonists
and antagonists are being developed as potential drugs.
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