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Extracellular cAMP inhibits D1 dopamine receptor expression in CAD catecholaminergic cells via A2a adenosine

Thuy Do1, Qian Sun, Annie Beuve

  • 1Department of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.

Journal of Neurochemistry
|January 27, 2007
PubMed

Insights

Extracellular cyclic AMP (cAMP) inhibits dopamine D1 receptor gene expression in neuronal cells. This novel mechanism involves adenosine A2a receptors and impacts D1 receptor regulation.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Dopamine D1 receptor gene expression is crucial for neuronal function and is altered in various conditions.
  • Extracellular factors regulating D1 receptor expression are not fully understood.

Purpose of the Study:

  • To investigate the role of extracellular factors, specifically cyclic AMP (cAMP), in modulating D1 dopamine receptor expression.
  • To elucidate the signaling pathways involved in extracellularly mediated regulation of D1 receptor gene expression.

Main Methods:

  • Utilized Cath.A Derived (CAD) catecholaminergic neuronal cell line.
  • Administered exogenous cAMP, AMP, and adenosine (ADO).
  • Assessed D1 receptor mRNA and protein levels.
  • Employed inhibitors of ecto-phosphodiesterase, ecto-nucleotidases, and alkaline phosphatase.
  • Investigated the role of adenosine A2a receptors.

Main Results:

  • Extracellular cAMP significantly decreased D1 receptor mRNA and protein levels in CAD cells.
  • Extracellular AMP also reduced D1 receptor mRNA levels.
  • The inhibitory effects of cAMP and AMP were partially mediated by ecto-nucleotidases and adenosine A2a receptors.
  • cGMP and ecto-phosphodiesterase inhibition blocked cAMP-induced D1 receptor mRNA decrease.

Conclusions:

  • Extracellular cAMP and its metabolite AMP inhibit D1 dopamine receptor gene expression in catecholaminergic neurons.
  • This inhibition is mediated through adenosine A2a receptors, revealing a novel regulatory pathway.
  • Findings suggest a new molecular mechanism linking adenosine receptor activation to D1 receptor expression modulation.

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