2-phenylaminoadenosine stimulates dopamine synthesis in rat forebrain in vitro and in vivo via adenosine A(2) receptors

The adenosine agonist 2-phenylaminoadenosine (PAD) stimulated tyrosine hydroxylase activity in rat striatum in vitro. This effect was selectively blocked by the A(2) antagonist 8-chlorostyrylcaffeine (CSC), suggesting an A(2) receptor-mediated mechanism. PAD also produced a corresponding increase in striatal adenylyl cyclase activity. Using an in vivo model that measures presynaptic effects of drugs at dopamine nerve terminals, intracerebroventricular administration of PAD to rats stimulated tyrosine hydroxylase activity in striatum in a manner that was selectively blocked by CSC. These results suggest that PAD stimulates adenylyl cyclase and tyrosine hydroxylase activity, with a corresponding increase in dopamine synthesis, by activation of presynaptic A(2)-type receptors in mammalian forebrain. (C) 1997 Elsevier Science B.V.