Pharmacology of adenosine A(2A) receptors

Adenosine A(2A) receptors, which have been cloned from several mammalian species, are activated by physiological concentrations of adenosine to stimulate the formation of cAMP and other mediators. The A(2A) receptors are found on neutrophil leukocytes, platelets, blood vessels and, very abundantly, on some cells in the CNS. In the caudate nucleus they coexist with dopamine D-2 receptors, and stimulation of A(2A) receptors causes a decrease in D-2 receptor-mediated neurotransmission. Thus, drugs that act on A(2A) receptors can be used to modify dopaminergic neurotransmission known to be important in neurological and psychiatric disorders. In this review, Ennio Ongini and Bertil Fredholm describe how recently developed potent and selective A(2A) receptor antagonists can be used to delineate the physiological and pathological processes regulated by A(2A) receptors. Results from in vitro and in vivo pharmacology studies strengthen the notion that A(2A) receptors are an interesting target for drug development.