2-Phenylaminoadenosine stimulates dopamine synthesis in rat forebrain in vitro and in vivo via adenosine A2 receptors.
The adenosine agonist 2-phenylaminoadenosine (PAD) stimulated tyrosine hydroxylase activity in rat striatum in vitro. This effect was selectively blocked by the A2 antagonist 8-chlorostyrylcaffeine (CSC), suggesting an A2 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 A2-type receptors in mammalian forebrain.
Choksi
N Y
NY
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360, USA.
Hussain
A
A
Booth
R G
RG
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D017072:Neostriatum / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D016548:Prosencephalon / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D014446:Tyrosine 3-Monooxygenase; D000262:Adenylyl Cyclases; C026708:2-phenylaminoadenosine; D000241:Adenosine; D004298:Dopamine