Extracellular cAMP inhibits D1 dopamine receptor expression in CAD catecholaminergic cells via A2a adenosine receptors.
The expression of D1 dopamine (DA) receptor gene is regulated during development, aging, and pathophysiology. The extracellular factors and signaling mechanisms that modulate the expression of D1 DA receptor have not been well characterized. Here, we present novel evidence that endogenous D1 DA receptor expression is inhibited by extracellular cAMP in the Cath.A Derived (CAD) catecholaminergic neuronal cell line. CAD cells express the multi-drug resistance protein 5 transporters and secrete cAMP. Addition of exogenous cAMP decreases D1 receptor mRNA and protein greater than fourfold in 24 h. The cAMP-induced decrease of D1 receptor mRNA levels is blocked by cGMP and by 1,3-dipropyl-8-(p-sulfo-phenyl)xanthine, an inhibitor of ecto-phosphodiestrase. Extracellular AMP, a metabolite of cAMP, also independently decreased D1 receptor mRNA levels. Inhibitors of ecto-nucleotidases, alpha,beta-methyleneadenosine 5'-di-phosphate and GMP, completely blocked the decrease of D1 receptor mRNA by extracellular cAMP, but only partially blocked the decrease induced by extracellular AMP. Levamisole, an inhibitor of tissue non-specific alkaline phosphatase, completely blocked the AMP-induced decrease of D1 receptor mRNA. The extracellular cAMP, AMP, and adenosine (ADO)-induced decrease in D1 receptor mRNA expression are mediated by A2a ADO receptor subtype. The results suggest a novel molecular mechanism linking activation of A2a ADO receptors with inhibition of D1 DA receptor expression.
Do
Thuy
T
Department of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.
Sun
Qian
Q
Beuve
Annie
A
Kuzhikandathil
Eldo V
EV
D000241:Adenosine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D006152:Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D017447:Receptors, Dopamine D1; D000242:Cyclic AMP; D006152:Cyclic GMP; D000241:Adenosine