Adenosine A(1) receptors (A(1)R) are able to form a heteromeric complex with P2Y(1) receptors (P2Y(1)R) that generates A(1)R with P2Y(1)R-like agonistic pharmacology. A potent P2Y(1)R agonist, adenosine 5'-O-(2-thiotriphosphate), binds the A(1)R binding pocket of the A(1)R/P2Y(1)R complex and inhibits adenylyl cyclase activity via G(i/o) protein. These mechanisms might be used to fine-tune purinergic inhibition locally at sites where there is a particular oligomerization structure between purinergic receptors and explain the undefined purinergic functions by adenosine and adenine nucleotides.